Clinical profile of hospitalized HIV-infected children in Bangladesh, a low-HIV-prevalence country Lubaba Shahrin1,2, Daniel T. Leung2,3, Nashaba Matin4, Chowdhury Ali Kawser5, Mohammed Moshtaq Pervez2, Mohammod Jobayer Chisti1 1
Centre for Nutrition and Food Security (CNFS), 2Centre for HIV/AIDS, 3Centre for Vaccine Science International Centre for Diarrheal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh, 4Imperial Healthcare NHS Trust, London, UK, 5Bangabandhu Sheikh Mujib Medical University, Bangladesh
Background: Bangladesh has a low HIV prevalence and data on the risk factors and clinical presentation of HIV-infected children are lacking. Objective: To describe the clinical characteristics of hospitalized HIV-infected children in Bangladesh and determine the factors associated with a low CD4 count. Methods: An anonymous, retrospective review was undertaken of the medical records of all patients admitted to the HIV unit of the iccdr,b Dhaka Hospital between February 2009 and July 2012. Demographic, clinical and laboratory data were extracted from the electronic medical record system. HIV-infected children with a low absolute CD4 count (,200 cells/ml) were compared with HIV-infected children with a CD4 count §200 cells/ml. Results: Of 266 HIV-infected patients, 24 were children (9%), 13 (54%) of whom were male. Ages ranged from 2 to 17 years (median 7). Of the 21 (88%) children who acquired the infection by vertical transmission, median age at diagnosis was 5.2 years, and the parents of 19 (79%) reported a history of external migration. Children commonly presented with prolonged fever (n514, 58%), recurrent cough (n514, 58%), failure to thrive (n511, 46%) and recurrent diarrhoea (n54, 17%). Six (25%) patients had tuberculosis, four (16.7%) had herpes zoster and four (16.7%) were diagnosed with Pneumocystis jirovecii pneumonia. One child died during hospitalization. Children with a low CD4 count (,200 cells/ml) more often had severe wasting (95% CI 1.2–453.97) and severe under-nutrition (95% CI 1.39–196.25) than those with a higher CD4 count*. Conclusion: The majority of HIV-infected children presenting to an inpatient speciality ward in Dhaka acquired HIV through vertical transmission, and most of the parents had a history of external migration. Further studies are needed to determine the optimal strategy for preventing mother-to-child transmission and for early identification and treatment of HIV-infected children in this low-prevalence country. Keywords: Bangladesh, Children, Low-HIV-prevalence country, HIV infection, CD4 count
Introduction The World Health Organization estimates that approximately 34 million people are living with human immunodeficiency (HIV) infection, including 3.3 million children.1,2 In 2012, c. 330,000 (280,000– 380,000) children were newly infected with HIV.2 The first case of HIV was detected in Bangladesh in 1989.4 Bangladesh is considered to be a low prevalence country with ,0.1% of infections in the general population (c. 7500 people).2 In 2012, an estimated 5.9% of all new HIV infections were in those
Correspondence to: L Shahrin, 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka 1212, Bangladesh. Fax: z880 2 882 3116/880 2 988 5657; email: [email protected]
ß W. S. Maney & Son Ltd 2014 DOI 10.1179/2046905513Y.0000000100
,15 years of age.3 However, data on the actual number of HIV-infected children in Bangladesh are limited. Information available from self-help groups of people living with HIV, a collection of nongovernmental organizations offering peer support and primary care to HIV-positive individuals in Bangladesh, shows that by 2010 54 children had been registered.5 A recent report from this institution demonstrated that 6% (7 of 109) of patients hospitalized with HIV were children aged 1.5– 9 years.6 Despite its low prevalence, from 2001to 2011, Bangladesh was one of only nine countries in which the HIV incidence increased by .25%.2 Factors such as the presence of high-risk groups, a lack of disease awareness in the general population,
Paediatrics and International Child Health
2014
VOL.
34
NO.
2
133
Shahrin et al.
HIV-infected children in Bangladesh
an increasingly mobile population, external migration and neighbouring countries with a high HIV prevalence7 make Bangladesh vulnerable to a largescale epidemic. The latest round (ninth) of serosurveillance further highlights the fact that in some border areas HIV prevalence in female sex workers is 1.6%,8 which could spread infection to the general population. In most developing countries, .90% of children acquire HIV by mother-to-child transmission (MTCT) including breast feeding.9 The lack of awareness of the clinical presentation of paediatric HIV and its associated risk factors, as well as a lack of HIV DNA PCR testing, has led to delayed diagnosis of HIV in infected children in Bangladesh.10 There is anecdotal evidence that the majority of HIV-positive children in Bangladesh have low CD4 counts at the time of diagnosis. Studies have demonstrated that the risk of death in HIV-infected children over 2 years of age increases sharply when the CD4% falls below 10%, and that mortality is even greater in such children,11,12 so prompt identification of infected children is crucial. There is a paucity of data on the clinical presentation of HIV in children in Bangladesh. Such information could lead to improvement in the identification, prevention and early initiation of treatment of infected children, and could inform policy decisions. Thus, the aim of this study is to describe the clinical characteristics of hospitalized HIV-infected children in Bangladesh and to determine the factors associated with presentation with a low CD4 count.
many different sources, including referrals from local NGOs (72%) and referrals from government (16%) and private (8%) hospitals.
Data collection De-identified demographic, clinical and laboratory data were extracted from electronic medical records and recorded in a database. When a child had been admitted before, only the first admission was included for analysis. Weight-for-height (WHZ), height-for-age (HAZ) and weight for age(WAZ) ,-3 were regarded as severe wasting, severe stunting and severe underweight, respectively. Parental HIV status and high-risk behaviour were explored to identify the mode of transmission. The World Health Organization’s (WHO) 2006 guidelines for clinical staging of patients were used.13
Ethical considerations The research was approved by the Research Review Committee of icddr,b.
Statistical analysis Data were entered into a database (SPSS version 17.0) for statistical analysis. The x2 test was used to determine differences between HIV-infected children with a CD4 count ,200 cells/ml and those with a CD4 count §200. A probability of ,0.05 was considered statistically significant. We determined strength of association by calculating the odds ratios and 95% confidence intervals. The clinical parameters are shown in Table 1.
Results Of 266 HIV-infected patients admitted to the facility between February 2008 and July 2012, 24 (9%) were children (13 males) with a median age of 7 years
Subjects and Methods Study design This was a retrospective medical record analysis of all hospitalized HIV-infected children in a specialized non-government inpatient facility (Jagori Unit) during February 2009 to July 2012. Some of the patients were included in a previous study.6
Table 1 Baseline children
Age group, y (range 2–17): ,5 5–15 .15 Religion Muslim Christian Hindu Parental external migration Mode of HIV transmission: Vertical Blood and blood products Sexual transmission Unknown
All children under 18 years of age with HIV confirmed by ELISA and Western Blot were included. HIV PCR is not routinely available in Bangladesh. However, as all HIV-positive patients were over 18 months, they were considered to be HIV-infected.
Study setting The Jagori Unit of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research Bangladesh (icddr,b) provides free treatment and logistic support to all HIV-positive patients. The unit was opened in 2002 to provide confidential voluntary counselling and testing (VCT) services in Bangladesh. The Jagori Inpatient Ward opened in May 2008 to provide clinical services to patients with HIV. Jagori receives patients from
Paediatrics and International Child Health
2014
VOL .
34
NO .
of
24
HIV-infected
No. (%)
Study population
134
characteristics
Recurrent hospitalization history CD4 count, cells/ml: ,10 10–49 50–100 101–199 .200
2
6 (25.0) 16 (66.7) 2 (8.3) 19 3 2 19
(79.2) (12.5) (8.3) (79.1)
21 1 1 1
(87.5) (4.2) (4.2) (4.2)
5 (20.8) 1 1 4 3 15
(4.1) (4.1) (16.7) (12.5) (62.5)
Shahrin et al.
(range 2–17). Table 2 shows the distribution of their baseline characteristics. Twenty-one (87.5%) children had been infected perinatally, 19 (79%) of whom also had an HIVpositive father. Median age at diagnosis was 5.2 years (IQR 18 months to 13 years). Of the three patients who had not been infected perinatally, one had a history of blood transfusion from an HIVpositive donor, one (a 17-year-old widow, formerly married to a returnee migrant worker) had suspected sexual transmission, and another had no history of transfusion or sexual intercourse and the parents were HIV-negative. After diagnosis, median time before hospitalization was 6.5 months (0–14). Only 10 of 20 children aged .5 years attended school. Seventeen (71%) children were receiving anti-retroviral therapy (ART) and 21 (88%) were receiving co-trimoxazole prophylaxis. Median CD4 count was 271 cells/ml (IQR 4–1632) and nine children had a CD4 count ,200 cells/ml. Estimates of CD4% were not available. Twenty-three (94%) patients were discharged and one patient died (6%). The cause of death was suspected Pneumocystis jirovecii pneumonia with sepsis. Discharged patients were referred to the aforementioned self-help groups for out-patient follow-up and long-term management of HIV. The clinical presentations of the children admitted are shown in Table 3. For those ,5 years of age, the mean WAZ was 22.1 and HAZ was 22.9. For those .5 years, the mean body mass index (BMI) was 12.6. Seventeen children had AIDS-defining illnesses (Table 3). The factors associated by univariate analysis with a low CD4 count (,200 cells/mm3) are shown in Table 4; these include severe wasting, severe undernutrition and use of antiretroviral therapy (ART).
Discussion Bangladesh has a low prevalence of HIV. Despite the low numbers of infected children documented, anecdotal reports suggest that most HIV-infected children in Bangladesh acquire the infection perinatally, but that, because of delay in recognition and diagnosis, treatment is often delayed, leading to poor outcomes.
Malnutrition is considered to be the most common manifestation in HIV-infected children in developing countries.14,15 In resource-limited settings, growth failure is a predictor of rapid disease progression.16 Studies from sub-Saharan Africa have demonstrated the association between malnutrition and a low baseline CD4 count with ART failure and mortality.17,18 An Indian study has documented high rates of malnutrition in HIV-infected children, irrespective of CD4 count.19 In this study, a strong association between severe malnutrition and low CD4 count was observed. In developing countries such as Bangladesh, the major precipitating factors of malnutrition, irrespective of HIV status, are food insecurity, low socioeconomic status, poor diet and parental illiteracy.20 Moreover, HIV infection contributes to childhood malnutrition through factors such as parental loss, disease-related anorexia, decreased absorption of nutrients and increased resting energy expenditure.21,22 Malnutrition is associated with deficiencies in the immune system, which can be improved with nutritional recovery;23 however, severely malnourished children with HIV infection continue to have lower CD4 counts, despite nutritional recovery,24 and thus nutritional rehabilitation should not delay initiation of ART. In HIV-infected children, ARV along with nutritional intervention demonstrated better outcomes than ARV alone.11,25 As severe malnutrition is a common presentation in HIV-infected children in Bangladesh, when associated with relevant risk factors, such as an HIV-infected parent/s with a migration history, those children should be selected for HIV screening. The majority of HIV-infected children had parents with a history of external migration. For many countries worldwide, Bangladesh is a major source of migrant workers and in 2011–12 they remitted $US11.65 billion from foreign currencies, the second highest contribution to the Bangladeshi gross domestic product.26 A study from this subcontinent reported that the spouses and partners of migrants are especially vulnerable to HIV infection owing to the greater possibility of extramarital relationships and low use of barrier contraceptives.27 A systemic review of labour migrants found that factors such as Table 3 AIDS-defining children
illnesses
Table 2 Clinical manifestations on initial presentation in 24 HIV-infected children Clinical signs/symptoms
No. (%)
Prolonged fever Recurrent cough Failure to thrive Recurrent diarrhoea Skin rash Oral thrush
14 14 11 4 4 3
(58) (58) (46) (17) (17) (13)
HIV-infected children in Bangladesh
in
24
hospitalized
No. (%) Tuberculosis Pulmonary Extrapulmonary Disseminated Herpes zoster Pneumocystis jirovecii pneumonia Chronic suppurative otitis media Not identified
Paediatrics and International Child Health
6 3 2 1 4 4 3 7
2014
(25.0) (50.0) (33.3) (16.7) (16.7) (16.7) (12.5) (29.0)
VOL .
34
NO .
2
135
Shahrin et al.
HIV-infected children in Bangladesh
Table 4 Relationship between clinical features during admission and CD4 count Parameter
CD4 count ,200 cells/ml n59 (%)
CD4 count §200 cells/ml n515 (%)
OR (95% CI)
P-value
Fever during admission Cough Diarrhoea Severe wasting Severe undernutrition Tuberculosis On antiretroviral therapy On PJP prophylaxis Fatal outcome
7 6 3 8 7 4 9 9 1
5 4 1 5 3 2 9 12 0
7.0 5.5 7.0 16.0 14.0 5.2 – – –
0.09 0.09 0.13 0.01 0.01 0.15 0.05 0.27 0.37
(78) (67) (37) (89) (78) (44) (100) (100) (11)
(33) (27) (7) (33) (20) (13) (60) (80)
(0.8–76.6) (0.7–52.1) (0.5–218.7) (1.3–453.9) (1.4–196.3) (0.53–62.16)
OR, odds ratio; CI, confidence interval
there is urgent need of national roll-out to other parts of Bangladesh with high levels of external migration. One limitation of this study is referral bias because it was a single-site, hospital-based study in a tertiary referral centre to which only the sickest children were admitted. Thus, the findings cannot be extrapolated to all HIV-infected children in Bangladesh. Secondly, the study was retrospective and the sample size was small. Furthermore, immunosuppression was assessed for absolute CD4 counts as CD4 percentages were unavailable. Nevertheless, this is an important clinical characterization of HIV-infected children in Bangladesh which provides insights which can facilitate the identification of HIV-infected children in this low-prevalence country.
cultural norms, family separation, difficult working conditions and poor social support were associated with the risk of HIV infection.28 All these factors are likely to contribute to delays in diagnosing HIV infection in the wives and children of migrants. In those who were infected perinatally, there was a median 5.2 years from birth to HIV diagnosis. Furthermore, despite free and universal primary school education in Bangladesh, only 10 of 20 school-aged children attended school at some point in their lives. We hypothesize that this is probably owing to chronic and/or recurrent illnesses and, for those already diagnosed with HIV, fear of refusal by school authorities to allow an HIV-infected child to attend school because of widespread discrimination against people living with HIV.29 Ultimately, early diagnosis and treatment of HIV-infected children, especially those of vulnerable parents such as migrant workers, could benefit the health and education of these children. Consistent with reports from neighbouring countries, the predominant mode of acquiring infection was MTCT.14,15,21 MTCT can be averted by appropriate prenatal care which offers voluntary counselling and testing (VCT) to all pregnant women and by the administration of antiretroviral therapy to HIVpositive mothers and their infants.30 A local pilot study of PMTCT in icddr,b identified 14 HIVpositive mothers who subsequently delivered 14 HIV-negative babies after appropriate intervention.5 The late age at diagnosis of perinatally infected children in this cohort (5.2 years) is higher than in reports from sub-Saharan Africa11 and underscores the need to identify infected mothers through appropriate screening strategies. A systematic PMTCT programme is still lacking in Bangladesh. Reasons for this include lack of government support, poor organization of antenatal services, religion and a presumption that the HIV prevalence is too low to warrant any action. Appropriate antenatal screening for HIV needs to be part of a package of interventions to facilitate achieving Millennium Development Goals 5 and 6. A single-site pilot in the Medical University Hospital, Dhaka has commenced, but
136
Paediatrics and International Child Health
2014
VOL .
34
NO .
References 1 UNAIDS. Global fact sheet: World AIDS Day, 2012. http:// www.unaids.org/en/media/unaids/contentassets/documents/epide miology/2012/gr2012/20121120_FactSheet_Global_en.pdf 2 UNAIDS. A Progress Report on the Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping their Mothers Alive. www.unaids.org/en/media/ …/JC2385_ProgressReportGlobalPlan_en.pdf 3 Waheed MA. World AIDS Day 2012: Presentation on HIV and AIDS Situation and National Responses. National AIDS/STD program. http://www.bdnasp.net/images/WAD%202012_30% 20November.ppt 4 Mamtaz AA. HIV/AIDS: response to the pandemic in Bangladesh. J Prev Soc Med. 1999;18:74–83. 5 UNICEF. HIV and AIDS in Bangladesh. http://www.unicef. org/bangladesh/HIV_AIDS%281%29.pdf 6 Matin N, Shahrin L, Pervez MM, Banu S, Ahmed D, Khatun M et al. Clinical profile of HIV/AIDS-infected patients admitted to a new specialist unit in Dhaka, Bangladesh – a low-prevalence country for HIV. J Health Popul Nutr. 2011;29:14–19. 7 Mondal NI, Takaku H, Ohkusa Y, Sugawara T, Okabe N. HIV/AIDS acquisition and transmission in Bangladesh: Turning to the concentrated epidemic. Jpn J Infect Dis. 2009;62:111–19. 8 National AIDS/STD Programme(NASP), Directorate General of Health Services (DGHS), Ministry of Health and Family Welfare (MOHFW). National HIV serological surveillence, 2011 Bangladesh: 9th Round Technical Report. http://aidsda tahub.org/en/reference-librarycols2/item/24018-national-hivserological-surveillance-bangladesh-9th-round-technical-reportiedcr-and-icddr-b-2011 9 World Health Organization. Towards Universal Access: Scaling Up Priority HIV/AIDS Interventions in the Health Sector: Progress Report, 2010. www.who.int/hiv/mediacentre/universal _access_progress_report_en.pdf 10 Gibb D, Newberry A, De Rossi A, Kaye S, Loveday C, MunozFernandez A, et al. HIV-1 viral load and CD4 cell count in untreated children with vertically acquired asymptomatic or mild disease. AIDS. 1998;12:F1–8.
2
Shahrin et al.
11 Desmonde S, Coffie P, Aka E, Amani-Bosse C, Messou E, Dabis F, et al. Severe morbidity and mortality in untreated HIV-infected children in a paediatric care programme in Abidjan, Cote d’Ivoire, 2004–2009. BMC Infect Dis. 2011; 11:1–12. 12 Dunn D. Short-term risk of disease progression in HIV-1infected children receiving no antiretroviral therapy or zidovudine monotherapy: a meta-analysis. Lancet. 2003;362:1605–11. 13 World Health Organization. WHO Case Definitions of HIV for Surveillance and Revised Clinical Staging and Immunological Classification of HIV-related Disease in Adults and Children. HIV/AIDS Programme. Strengthening Health Services to Fight HIV/AIDS. www.who.int/hiv/pub/guidelines/HIVstaging150307. pdf. 14 Lodha R, Upadhyay A, Kapoor V, Kabra SK. Clinical profile and natural history of children with HIV infection. Indian J Pediatr. 2006;73:201–4. 15 Rajasekaran S, Jeyaseelan L, Raja K, Ravichandran N. Demographic and clinical profile of HIV infected children accessing care at Tambaram, Chennai, India. Indian J Med Res. 2009;129:42–9. 16 Chearskul S, Chotpitayasunondh T, Simonds RJ, Wanprapar N, Waranawat N, Punpanich W, et al. Survival, disease manifestations, and early predictors of disease progression among children with perinatal human immunodeficiency virus infection in Thailand. Pediatrics. 2002;110:1–6. 17 Bacha T, Tilahun B, Worku A. Predictors of treatment failure and time to detection and switching in HIV-infected Ethiopian children receiving firstline anti-retroviral therapy. BMC Infect Dis. 2012;12:1–8. 18 Naidoo R, Rennert W, Lung A, Naidoo K, McKerrow N. The influence of nutritional status on the response to HAART in HIV-infected children in South Africa. Pediatr Infect Dis J. 2010;29:511–13. 19 Padmapriyadarsini C, Pooranagangadevi N, Chandrasekaran K, Subramanyan S, Thiruvalluvan C, Bhavani PK, et al. Prevalence of underweight, stunting, and wasting among children infected with human immunodeficiency virus in South India. Int J Pediatr. 2009;2009:1–5.
HIV-infected children in Bangladesh
20 Ahmed T, Hossain M, Sanin KI. Global burden of maternal and child undernutrition and micronutrient deficiencies. Ann Nutr Metab. 2012;61 (suppl 1):8–17. 21 Shah SR, Tullu MS, Kamat JR. Clinical profile of pediatric HIV infection from India. Arch Med Res. 2005;36:24–31. 22 Musoke PM, Fergusson P. Severe malnutrition and metabolic complications of HIV-infected children in the antiretroviral era: clinical care and management in resource-limited settings. Am J Clin Nutr. 2011;94:1716–20S. 23 Duggal S, Chugh TD, Duggal AK. HIV and malnutrition: effects on immune system. Clin Dev Immunol. 2012;2012:1–8. 24 Hughes SM, Amadi B, Mwiya M, Nkamba H, Mulundu G, Tomkins A, et al. CD4 counts decline despite nutritional recovery in HIV-infected Zambian children with severe malnutrition. Pediatrics. 2009;123:e347–51. 25 Sunguya BF, Poudel KC, Otsuka K, Yasuoka J, Mlunde LB, Urassa DP, et al. Undernutrition among HIV-positive children in Dar es Salaam, Tanzania: antiretroviral therapy alone is not enough. BMC Public Health. 2011;11:869. 26 International Organization for Migration (IOM). Situation Analysis on Migration and HIV in Bangladesh. http:// hpnconsortium.org/materials/material-detail/69/1/2. 27 International Organization for Migration (IOM). HIV and Bangladeshi Women Migrant Workers: An assessment of Vulnerabilities and Gaps in Services. http://www.emn.at/en/ hiv-and-bangladeshi-women-migrant-workers-an-assessmentof-vulnerabilities-and-gaps-in-services 28 Weine SM, Kashuba AB. Labor migration and HIV risk: a systematic review of the literature. AIDS Behav. 2012;16:1605– 21. 29 Hasan MT, Nath SR, Khan NS, Akram O, Gomes TM, Rashid SF. Internalized HIV/AIDS-related stigma in a sample of HIVpositive people in Bangladesh.J Health Popul Nutr. 2012;30: 22–30. 30 Tudor Car L, Brusamento S, Elmoniry H, van Velthoven MH, Pape UJ, Welch V, et al. The uptake of integrated perinatal prevention of mother-to-child HIV transmission programs in low- and middle-income countries: a systematic review. PloS One. 2013;8:1–16.
Paediatrics and International Child Health
2014
VOL .
34
NO .
2
137
Centre for Nutrition and Food Security (CNFS), 2Centre for HIV/AIDS, 3Centre for Vaccine Science International Centre for Diarrheal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh, 4Imperial Healthcare NHS Trust, London, UK, 5Bangabandhu Sheikh Mujib Medical University, Bangladesh
Background: Bangladesh has a low HIV prevalence and data on the risk factors and clinical presentation of HIV-infected children are lacking. Objective: To describe the clinical characteristics of hospitalized HIV-infected children in Bangladesh and determine the factors associated with a low CD4 count. Methods: An anonymous, retrospective review was undertaken of the medical records of all patients admitted to the HIV unit of the iccdr,b Dhaka Hospital between February 2009 and July 2012. Demographic, clinical and laboratory data were extracted from the electronic medical record system. HIV-infected children with a low absolute CD4 count (,200 cells/ml) were compared with HIV-infected children with a CD4 count §200 cells/ml. Results: Of 266 HIV-infected patients, 24 were children (9%), 13 (54%) of whom were male. Ages ranged from 2 to 17 years (median 7). Of the 21 (88%) children who acquired the infection by vertical transmission, median age at diagnosis was 5.2 years, and the parents of 19 (79%) reported a history of external migration. Children commonly presented with prolonged fever (n514, 58%), recurrent cough (n514, 58%), failure to thrive (n511, 46%) and recurrent diarrhoea (n54, 17%). Six (25%) patients had tuberculosis, four (16.7%) had herpes zoster and four (16.7%) were diagnosed with Pneumocystis jirovecii pneumonia. One child died during hospitalization. Children with a low CD4 count (,200 cells/ml) more often had severe wasting (95% CI 1.2–453.97) and severe under-nutrition (95% CI 1.39–196.25) than those with a higher CD4 count*. Conclusion: The majority of HIV-infected children presenting to an inpatient speciality ward in Dhaka acquired HIV through vertical transmission, and most of the parents had a history of external migration. Further studies are needed to determine the optimal strategy for preventing mother-to-child transmission and for early identification and treatment of HIV-infected children in this low-prevalence country. Keywords: Bangladesh, Children, Low-HIV-prevalence country, HIV infection, CD4 count
Introduction The World Health Organization estimates that approximately 34 million people are living with human immunodeficiency (HIV) infection, including 3.3 million children.1,2 In 2012, c. 330,000 (280,000– 380,000) children were newly infected with HIV.2 The first case of HIV was detected in Bangladesh in 1989.4 Bangladesh is considered to be a low prevalence country with ,0.1% of infections in the general population (c. 7500 people).2 In 2012, an estimated 5.9% of all new HIV infections were in those
Correspondence to: L Shahrin, 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka 1212, Bangladesh. Fax: z880 2 882 3116/880 2 988 5657; email: [email protected]
ß W. S. Maney & Son Ltd 2014 DOI 10.1179/2046905513Y.0000000100
,15 years of age.3 However, data on the actual number of HIV-infected children in Bangladesh are limited. Information available from self-help groups of people living with HIV, a collection of nongovernmental organizations offering peer support and primary care to HIV-positive individuals in Bangladesh, shows that by 2010 54 children had been registered.5 A recent report from this institution demonstrated that 6% (7 of 109) of patients hospitalized with HIV were children aged 1.5– 9 years.6 Despite its low prevalence, from 2001to 2011, Bangladesh was one of only nine countries in which the HIV incidence increased by .25%.2 Factors such as the presence of high-risk groups, a lack of disease awareness in the general population,
Paediatrics and International Child Health
2014
VOL.
34
NO.
2
133
Shahrin et al.
HIV-infected children in Bangladesh
an increasingly mobile population, external migration and neighbouring countries with a high HIV prevalence7 make Bangladesh vulnerable to a largescale epidemic. The latest round (ninth) of serosurveillance further highlights the fact that in some border areas HIV prevalence in female sex workers is 1.6%,8 which could spread infection to the general population. In most developing countries, .90% of children acquire HIV by mother-to-child transmission (MTCT) including breast feeding.9 The lack of awareness of the clinical presentation of paediatric HIV and its associated risk factors, as well as a lack of HIV DNA PCR testing, has led to delayed diagnosis of HIV in infected children in Bangladesh.10 There is anecdotal evidence that the majority of HIV-positive children in Bangladesh have low CD4 counts at the time of diagnosis. Studies have demonstrated that the risk of death in HIV-infected children over 2 years of age increases sharply when the CD4% falls below 10%, and that mortality is even greater in such children,11,12 so prompt identification of infected children is crucial. There is a paucity of data on the clinical presentation of HIV in children in Bangladesh. Such information could lead to improvement in the identification, prevention and early initiation of treatment of infected children, and could inform policy decisions. Thus, the aim of this study is to describe the clinical characteristics of hospitalized HIV-infected children in Bangladesh and to determine the factors associated with presentation with a low CD4 count.
many different sources, including referrals from local NGOs (72%) and referrals from government (16%) and private (8%) hospitals.
Data collection De-identified demographic, clinical and laboratory data were extracted from electronic medical records and recorded in a database. When a child had been admitted before, only the first admission was included for analysis. Weight-for-height (WHZ), height-for-age (HAZ) and weight for age(WAZ) ,-3 were regarded as severe wasting, severe stunting and severe underweight, respectively. Parental HIV status and high-risk behaviour were explored to identify the mode of transmission. The World Health Organization’s (WHO) 2006 guidelines for clinical staging of patients were used.13
Ethical considerations The research was approved by the Research Review Committee of icddr,b.
Statistical analysis Data were entered into a database (SPSS version 17.0) for statistical analysis. The x2 test was used to determine differences between HIV-infected children with a CD4 count ,200 cells/ml and those with a CD4 count §200. A probability of ,0.05 was considered statistically significant. We determined strength of association by calculating the odds ratios and 95% confidence intervals. The clinical parameters are shown in Table 1.
Results Of 266 HIV-infected patients admitted to the facility between February 2008 and July 2012, 24 (9%) were children (13 males) with a median age of 7 years
Subjects and Methods Study design This was a retrospective medical record analysis of all hospitalized HIV-infected children in a specialized non-government inpatient facility (Jagori Unit) during February 2009 to July 2012. Some of the patients were included in a previous study.6
Table 1 Baseline children
Age group, y (range 2–17): ,5 5–15 .15 Religion Muslim Christian Hindu Parental external migration Mode of HIV transmission: Vertical Blood and blood products Sexual transmission Unknown
All children under 18 years of age with HIV confirmed by ELISA and Western Blot were included. HIV PCR is not routinely available in Bangladesh. However, as all HIV-positive patients were over 18 months, they were considered to be HIV-infected.
Study setting The Jagori Unit of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research Bangladesh (icddr,b) provides free treatment and logistic support to all HIV-positive patients. The unit was opened in 2002 to provide confidential voluntary counselling and testing (VCT) services in Bangladesh. The Jagori Inpatient Ward opened in May 2008 to provide clinical services to patients with HIV. Jagori receives patients from
Paediatrics and International Child Health
2014
VOL .
34
NO .
of
24
HIV-infected
No. (%)
Study population
134
characteristics
Recurrent hospitalization history CD4 count, cells/ml: ,10 10–49 50–100 101–199 .200
2
6 (25.0) 16 (66.7) 2 (8.3) 19 3 2 19
(79.2) (12.5) (8.3) (79.1)
21 1 1 1
(87.5) (4.2) (4.2) (4.2)
5 (20.8) 1 1 4 3 15
(4.1) (4.1) (16.7) (12.5) (62.5)
Shahrin et al.
(range 2–17). Table 2 shows the distribution of their baseline characteristics. Twenty-one (87.5%) children had been infected perinatally, 19 (79%) of whom also had an HIVpositive father. Median age at diagnosis was 5.2 years (IQR 18 months to 13 years). Of the three patients who had not been infected perinatally, one had a history of blood transfusion from an HIVpositive donor, one (a 17-year-old widow, formerly married to a returnee migrant worker) had suspected sexual transmission, and another had no history of transfusion or sexual intercourse and the parents were HIV-negative. After diagnosis, median time before hospitalization was 6.5 months (0–14). Only 10 of 20 children aged .5 years attended school. Seventeen (71%) children were receiving anti-retroviral therapy (ART) and 21 (88%) were receiving co-trimoxazole prophylaxis. Median CD4 count was 271 cells/ml (IQR 4–1632) and nine children had a CD4 count ,200 cells/ml. Estimates of CD4% were not available. Twenty-three (94%) patients were discharged and one patient died (6%). The cause of death was suspected Pneumocystis jirovecii pneumonia with sepsis. Discharged patients were referred to the aforementioned self-help groups for out-patient follow-up and long-term management of HIV. The clinical presentations of the children admitted are shown in Table 3. For those ,5 years of age, the mean WAZ was 22.1 and HAZ was 22.9. For those .5 years, the mean body mass index (BMI) was 12.6. Seventeen children had AIDS-defining illnesses (Table 3). The factors associated by univariate analysis with a low CD4 count (,200 cells/mm3) are shown in Table 4; these include severe wasting, severe undernutrition and use of antiretroviral therapy (ART).
Discussion Bangladesh has a low prevalence of HIV. Despite the low numbers of infected children documented, anecdotal reports suggest that most HIV-infected children in Bangladesh acquire the infection perinatally, but that, because of delay in recognition and diagnosis, treatment is often delayed, leading to poor outcomes.
Malnutrition is considered to be the most common manifestation in HIV-infected children in developing countries.14,15 In resource-limited settings, growth failure is a predictor of rapid disease progression.16 Studies from sub-Saharan Africa have demonstrated the association between malnutrition and a low baseline CD4 count with ART failure and mortality.17,18 An Indian study has documented high rates of malnutrition in HIV-infected children, irrespective of CD4 count.19 In this study, a strong association between severe malnutrition and low CD4 count was observed. In developing countries such as Bangladesh, the major precipitating factors of malnutrition, irrespective of HIV status, are food insecurity, low socioeconomic status, poor diet and parental illiteracy.20 Moreover, HIV infection contributes to childhood malnutrition through factors such as parental loss, disease-related anorexia, decreased absorption of nutrients and increased resting energy expenditure.21,22 Malnutrition is associated with deficiencies in the immune system, which can be improved with nutritional recovery;23 however, severely malnourished children with HIV infection continue to have lower CD4 counts, despite nutritional recovery,24 and thus nutritional rehabilitation should not delay initiation of ART. In HIV-infected children, ARV along with nutritional intervention demonstrated better outcomes than ARV alone.11,25 As severe malnutrition is a common presentation in HIV-infected children in Bangladesh, when associated with relevant risk factors, such as an HIV-infected parent/s with a migration history, those children should be selected for HIV screening. The majority of HIV-infected children had parents with a history of external migration. For many countries worldwide, Bangladesh is a major source of migrant workers and in 2011–12 they remitted $US11.65 billion from foreign currencies, the second highest contribution to the Bangladeshi gross domestic product.26 A study from this subcontinent reported that the spouses and partners of migrants are especially vulnerable to HIV infection owing to the greater possibility of extramarital relationships and low use of barrier contraceptives.27 A systemic review of labour migrants found that factors such as Table 3 AIDS-defining children
illnesses
Table 2 Clinical manifestations on initial presentation in 24 HIV-infected children Clinical signs/symptoms
No. (%)
Prolonged fever Recurrent cough Failure to thrive Recurrent diarrhoea Skin rash Oral thrush
14 14 11 4 4 3
(58) (58) (46) (17) (17) (13)
HIV-infected children in Bangladesh
in
24
hospitalized
No. (%) Tuberculosis Pulmonary Extrapulmonary Disseminated Herpes zoster Pneumocystis jirovecii pneumonia Chronic suppurative otitis media Not identified
Paediatrics and International Child Health
6 3 2 1 4 4 3 7
2014
(25.0) (50.0) (33.3) (16.7) (16.7) (16.7) (12.5) (29.0)
VOL .
34
NO .
2
135
Shahrin et al.
HIV-infected children in Bangladesh
Table 4 Relationship between clinical features during admission and CD4 count Parameter
CD4 count ,200 cells/ml n59 (%)
CD4 count §200 cells/ml n515 (%)
OR (95% CI)
P-value
Fever during admission Cough Diarrhoea Severe wasting Severe undernutrition Tuberculosis On antiretroviral therapy On PJP prophylaxis Fatal outcome
7 6 3 8 7 4 9 9 1
5 4 1 5 3 2 9 12 0
7.0 5.5 7.0 16.0 14.0 5.2 – – –
0.09 0.09 0.13 0.01 0.01 0.15 0.05 0.27 0.37
(78) (67) (37) (89) (78) (44) (100) (100) (11)
(33) (27) (7) (33) (20) (13) (60) (80)
(0.8–76.6) (0.7–52.1) (0.5–218.7) (1.3–453.9) (1.4–196.3) (0.53–62.16)
OR, odds ratio; CI, confidence interval
there is urgent need of national roll-out to other parts of Bangladesh with high levels of external migration. One limitation of this study is referral bias because it was a single-site, hospital-based study in a tertiary referral centre to which only the sickest children were admitted. Thus, the findings cannot be extrapolated to all HIV-infected children in Bangladesh. Secondly, the study was retrospective and the sample size was small. Furthermore, immunosuppression was assessed for absolute CD4 counts as CD4 percentages were unavailable. Nevertheless, this is an important clinical characterization of HIV-infected children in Bangladesh which provides insights which can facilitate the identification of HIV-infected children in this low-prevalence country.
cultural norms, family separation, difficult working conditions and poor social support were associated with the risk of HIV infection.28 All these factors are likely to contribute to delays in diagnosing HIV infection in the wives and children of migrants. In those who were infected perinatally, there was a median 5.2 years from birth to HIV diagnosis. Furthermore, despite free and universal primary school education in Bangladesh, only 10 of 20 school-aged children attended school at some point in their lives. We hypothesize that this is probably owing to chronic and/or recurrent illnesses and, for those already diagnosed with HIV, fear of refusal by school authorities to allow an HIV-infected child to attend school because of widespread discrimination against people living with HIV.29 Ultimately, early diagnosis and treatment of HIV-infected children, especially those of vulnerable parents such as migrant workers, could benefit the health and education of these children. Consistent with reports from neighbouring countries, the predominant mode of acquiring infection was MTCT.14,15,21 MTCT can be averted by appropriate prenatal care which offers voluntary counselling and testing (VCT) to all pregnant women and by the administration of antiretroviral therapy to HIVpositive mothers and their infants.30 A local pilot study of PMTCT in icddr,b identified 14 HIVpositive mothers who subsequently delivered 14 HIV-negative babies after appropriate intervention.5 The late age at diagnosis of perinatally infected children in this cohort (5.2 years) is higher than in reports from sub-Saharan Africa11 and underscores the need to identify infected mothers through appropriate screening strategies. A systematic PMTCT programme is still lacking in Bangladesh. Reasons for this include lack of government support, poor organization of antenatal services, religion and a presumption that the HIV prevalence is too low to warrant any action. Appropriate antenatal screening for HIV needs to be part of a package of interventions to facilitate achieving Millennium Development Goals 5 and 6. A single-site pilot in the Medical University Hospital, Dhaka has commenced, but
136
Paediatrics and International Child Health
2014
VOL .
34
NO .
References 1 UNAIDS. Global fact sheet: World AIDS Day, 2012. http:// www.unaids.org/en/media/unaids/contentassets/documents/epide miology/2012/gr2012/20121120_FactSheet_Global_en.pdf 2 UNAIDS. A Progress Report on the Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping their Mothers Alive. www.unaids.org/en/media/ …/JC2385_ProgressReportGlobalPlan_en.pdf 3 Waheed MA. World AIDS Day 2012: Presentation on HIV and AIDS Situation and National Responses. National AIDS/STD program. http://www.bdnasp.net/images/WAD%202012_30% 20November.ppt 4 Mamtaz AA. HIV/AIDS: response to the pandemic in Bangladesh. J Prev Soc Med. 1999;18:74–83. 5 UNICEF. HIV and AIDS in Bangladesh. http://www.unicef. org/bangladesh/HIV_AIDS%281%29.pdf 6 Matin N, Shahrin L, Pervez MM, Banu S, Ahmed D, Khatun M et al. Clinical profile of HIV/AIDS-infected patients admitted to a new specialist unit in Dhaka, Bangladesh – a low-prevalence country for HIV. J Health Popul Nutr. 2011;29:14–19. 7 Mondal NI, Takaku H, Ohkusa Y, Sugawara T, Okabe N. HIV/AIDS acquisition and transmission in Bangladesh: Turning to the concentrated epidemic. Jpn J Infect Dis. 2009;62:111–19. 8 National AIDS/STD Programme(NASP), Directorate General of Health Services (DGHS), Ministry of Health and Family Welfare (MOHFW). National HIV serological surveillence, 2011 Bangladesh: 9th Round Technical Report. http://aidsda tahub.org/en/reference-librarycols2/item/24018-national-hivserological-surveillance-bangladesh-9th-round-technical-reportiedcr-and-icddr-b-2011 9 World Health Organization. Towards Universal Access: Scaling Up Priority HIV/AIDS Interventions in the Health Sector: Progress Report, 2010. www.who.int/hiv/mediacentre/universal _access_progress_report_en.pdf 10 Gibb D, Newberry A, De Rossi A, Kaye S, Loveday C, MunozFernandez A, et al. HIV-1 viral load and CD4 cell count in untreated children with vertically acquired asymptomatic or mild disease. AIDS. 1998;12:F1–8.
2
Shahrin et al.
11 Desmonde S, Coffie P, Aka E, Amani-Bosse C, Messou E, Dabis F, et al. Severe morbidity and mortality in untreated HIV-infected children in a paediatric care programme in Abidjan, Cote d’Ivoire, 2004–2009. BMC Infect Dis. 2011; 11:1–12. 12 Dunn D. Short-term risk of disease progression in HIV-1infected children receiving no antiretroviral therapy or zidovudine monotherapy: a meta-analysis. Lancet. 2003;362:1605–11. 13 World Health Organization. WHO Case Definitions of HIV for Surveillance and Revised Clinical Staging and Immunological Classification of HIV-related Disease in Adults and Children. HIV/AIDS Programme. Strengthening Health Services to Fight HIV/AIDS. www.who.int/hiv/pub/guidelines/HIVstaging150307. pdf. 14 Lodha R, Upadhyay A, Kapoor V, Kabra SK. Clinical profile and natural history of children with HIV infection. Indian J Pediatr. 2006;73:201–4. 15 Rajasekaran S, Jeyaseelan L, Raja K, Ravichandran N. Demographic and clinical profile of HIV infected children accessing care at Tambaram, Chennai, India. Indian J Med Res. 2009;129:42–9. 16 Chearskul S, Chotpitayasunondh T, Simonds RJ, Wanprapar N, Waranawat N, Punpanich W, et al. Survival, disease manifestations, and early predictors of disease progression among children with perinatal human immunodeficiency virus infection in Thailand. Pediatrics. 2002;110:1–6. 17 Bacha T, Tilahun B, Worku A. Predictors of treatment failure and time to detection and switching in HIV-infected Ethiopian children receiving firstline anti-retroviral therapy. BMC Infect Dis. 2012;12:1–8. 18 Naidoo R, Rennert W, Lung A, Naidoo K, McKerrow N. The influence of nutritional status on the response to HAART in HIV-infected children in South Africa. Pediatr Infect Dis J. 2010;29:511–13. 19 Padmapriyadarsini C, Pooranagangadevi N, Chandrasekaran K, Subramanyan S, Thiruvalluvan C, Bhavani PK, et al. Prevalence of underweight, stunting, and wasting among children infected with human immunodeficiency virus in South India. Int J Pediatr. 2009;2009:1–5.
HIV-infected children in Bangladesh
20 Ahmed T, Hossain M, Sanin KI. Global burden of maternal and child undernutrition and micronutrient deficiencies. Ann Nutr Metab. 2012;61 (suppl 1):8–17. 21 Shah SR, Tullu MS, Kamat JR. Clinical profile of pediatric HIV infection from India. Arch Med Res. 2005;36:24–31. 22 Musoke PM, Fergusson P. Severe malnutrition and metabolic complications of HIV-infected children in the antiretroviral era: clinical care and management in resource-limited settings. Am J Clin Nutr. 2011;94:1716–20S. 23 Duggal S, Chugh TD, Duggal AK. HIV and malnutrition: effects on immune system. Clin Dev Immunol. 2012;2012:1–8. 24 Hughes SM, Amadi B, Mwiya M, Nkamba H, Mulundu G, Tomkins A, et al. CD4 counts decline despite nutritional recovery in HIV-infected Zambian children with severe malnutrition. Pediatrics. 2009;123:e347–51. 25 Sunguya BF, Poudel KC, Otsuka K, Yasuoka J, Mlunde LB, Urassa DP, et al. Undernutrition among HIV-positive children in Dar es Salaam, Tanzania: antiretroviral therapy alone is not enough. BMC Public Health. 2011;11:869. 26 International Organization for Migration (IOM). Situation Analysis on Migration and HIV in Bangladesh. http:// hpnconsortium.org/materials/material-detail/69/1/2. 27 International Organization for Migration (IOM). HIV and Bangladeshi Women Migrant Workers: An assessment of Vulnerabilities and Gaps in Services. http://www.emn.at/en/ hiv-and-bangladeshi-women-migrant-workers-an-assessmentof-vulnerabilities-and-gaps-in-services 28 Weine SM, Kashuba AB. Labor migration and HIV risk: a systematic review of the literature. AIDS Behav. 2012;16:1605– 21. 29 Hasan MT, Nath SR, Khan NS, Akram O, Gomes TM, Rashid SF. Internalized HIV/AIDS-related stigma in a sample of HIVpositive people in Bangladesh.J Health Popul Nutr. 2012;30: 22–30. 30 Tudor Car L, Brusamento S, Elmoniry H, van Velthoven MH, Pape UJ, Welch V, et al. The uptake of integrated perinatal prevention of mother-to-child HIV transmission programs in low- and middle-income countries: a systematic review. PloS One. 2013;8:1–16.
Paediatrics and International Child Health
2014
VOL .
34
NO .
2
137
