|Year : 2019 | Volume
| Issue : 3 | Page : 1232-1234
Increased household exposure to respiratory pathogens in HIV exposed uninfected children due to maternal HIV
Tila Khan, Ranjan S Das, Sangeeta D Bhattacharya
School of Medical Science and Technology, Indian Institute of Technology (IIT) - Kharagpur, Kharagpur, West Bengal, India
|Date of Web Publication||27-Mar-2019|
Prof. Sangeeta D Bhattacharya
School of Medical Science and Technology, Indian Institute of Technology (IIT) - Kharagpur, Kharagpur - 721 302, West Bengal
Source of Support: None, Conflict of Interest: None
Little is known about household exposures to respiratory pathogens in HIV-exposed uninfected children (HEU) in Indian families. This case series investigates the nasopharyngeal carriage of Streptococcus pneumoniae, Staphylococcus aureus, and respiratory viruses at multiple points in three mother child pairs: (1) an HIV-infected child and mother, (2) an HEU child and HIV-infected mother, and (3) an HIV-unexposed uninfected (HUU) child and mother. Nasopharyngeal carriage densities of Streptococcus pneumoniae and Staphylococcus aureus were higher in mothers and children living in HIV-affected households, regardless of the child's HIV status. Maternal HIV and ART status impact these household exposures.
Keywords: Antiretroviral therapy, HIV-exposed uninfected children; household exposure, maternal HIV, respiratory microbes
|How to cite this article:|
Khan T, Das RS, Bhattacharya SD. Increased household exposure to respiratory pathogens in HIV exposed uninfected children due to maternal HIV. J Family Med Prim Care 2019;8:1232-4
|How to cite this URL:|
Khan T, Das RS, Bhattacharya SD. Increased household exposure to respiratory pathogens in HIV exposed uninfected children due to maternal HIV. J Family Med Prim Care [serial online] 2019 [cited 2019 Dec 15];8:1232-4. Available from: http://www.jfmpc.com/text.asp?2019/8/3/1232/254842
| Introduction|| |
Compared with unexposed children, HEU children are at 70% increased risk of all-cause mortality, specifically from lower respiratory tract infections. Respiratory pathogen exposures of HEU children living in HIV-affected Indian households are unknown. This case series is unique in presenting carriage information across time in three households: (1) an HIV-infected child and his mother (2) an HEU child and his mother, and (3) an HIV-uninfected child and his mother from rural India.
| Case History|| |
We present a case series of three families with similar socioeconomic backgrounds who participated in a vaccine study on the impact of Haemophilus influenzae type b (Hib) and pneumococcal conjugate vaccines (PCV) on nasopharyngeal carriage in children and parents affected by HIV in West Bengal, India. Case 1 is a child living with HIV (CLH); case 2 is an HEU child; and case 3 is an HUU child. We determined nasopharyngeal carriage of Streptococcus pneumoniae, Staphylococcus aureus, and respiratory viruses by culture and PCR in children and their mothers at multiple points between February 2012 and October 2014.
Case 1: HIV infected child and mother
A 4-year-old boy with perinatal HIV was enrolled in March, 2012, with a baseline CD4 count of 889 cells/mm 3 and viral load of 5560 copies/mL. He was on trimethoprim/sulfamethoxazole (TMP/SMX) but not on ART. He lived with his mother who was HIV infected, four adults, and six children, in a four-room mud house. They used pond water for bathing, tap water for drinking, and cow dung for cooking. He attended school. Their family income was INR 3000--5000/month. His father had died of HIV and tuberculosis (TB). His mother, treated for TB in the past, was on ART. This child had never had TB prophylaxis or treatment. He had received BCG, DPT1-4, OPV1-4, and measles vaccines. His baseline weight-for-age Z-score (WAZ) was −4.6 and height-for-age was Z-scores (HAZ) −2.5. Pneumococcus was isolated three times, the highest carriage density was 3.77 × 108 copies/ml, S. aureus twice, and Hib once [Table 1]. Both he and his mother had dual colonization with pneumococcus and S. aureus. His mother had S. aureus carriage at two other times. The highest carriage density for pneumococcus for mother was 5.56 × 103 copies/mL. Pneumococcal isolates were resistant to tetracycline, ofloxacin, azithromycin, and TMP/SMX. No respiratory virus was detected.
|Table 1: Comparison of nasopharyngeal colonization of Streptococcus pneumoniae, Staphylococcus aureus and Haemophilus influenzae type b and their density (copies/mL), and viral activity in HIV-infected child and his mother, HIV-exposed uninfected child and his mother, and, HIV-unexposed uninfected child and his mother at different time points (V1--V6) during the entire study period|
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Case 2: HEU child and HIV-infected mother
A 3.75-year-old boy born to HIV-infected parents by normal home delivery was enrolled in April, 2012, and misclassified as HIV positive. His CD4 count was 748 cells/mm 3. He was on TMP/SMX. He lived with his parents who were both HIV infected, his father was on ART, but his mother was not. He was breastfed till 8 months.
At study entry, HIV plasma viral load showed undetectable HIV and a repeat serologic HIV test confirmed that he was indeed HIV uninfected. He had gotten BCG, DPT1-5, OPV1-4, measles1, and hepatitis B1-3. He lived with four adults in a two-room brick house. Tube well was used for drinking and bathing and coal and wood for cooking. He attended school. Their medium income was INR 3000--5000/month. His baseline WAZ was −0.86 and HAZ was −0.97.
Pneumococcus was isolated at baseline with carriage density of 1.1 × 1010 copies/mL [Table 1]. He had dual colonization of pneumococcus and S. aureus twice. In four of six visits, he had rhinorrhoea and cough. Rhinovirus, adenovirus, and parainfluenza 4 virus were isolated at different times.
His mother had pneumococcal carriage at five of six visits with carriage density of 1.43 × 1010 copies/mL and had dual colonization with S. aureus in three [Table 1]. Pneumococcal isolates were resistant to tetracycline, erythromycin, ofloxacin, and TMP/SMX.
Case 3: HUU child and mother
A 3-year-old boy born to HIV-uninfected parents by normal institutional delivery was enrolled in October, 2013. He was breastfed till 3. He attended school. He had received BCG, DPT1-4, OPV1-4, measles1, hepatitis B-1, and Japanese encephalitis. He lived with his parents, two adults, and two children. They used well water for bathing and drinking, cow dung as cooking fuel, and lived in a mud house. His baseline WAZ was −1.25 and HAZ was −0.62. The family's income was INR 3000--5000/month.
He had one time pneumococcal carriage at 2.90 × 105 copies/mL [Table 1]. His mother had respiratory syncytial virus isolated once.
| Discussion|| |
Nasopharyngeal carriage densities of pneumococcus and S. aureus were higher in both mothers and children living in HIV-affected households, regardless of the child's HIV status. Case 2, the HEU child, had more frequent bacterial and viral carriage. The mother of the HEU child, not on ART, was frequently colonized with high densities of pneumococcus and S. aureus compared with the mother of case 1 who was on ART.
Maternal HIV has a profound impact on the health outcomes of exposed offspring. HEU children have increased mortality if their mothers have high HIV viral loads and CD4 counts <350 cells/mm 3. In Mozambique, HEU children had two times the mortality of HUU children, increased hospitalizations, and higher rates of malnutrition.
HEU children have increased morbidity and mortality from lower respiratory tract infections., Maternal HIV impacts lung development and respiratory health in offspring. Exposure to HIV in utero especially in mothers, who are untreated as case 2, leads infants to have increased lymphocyte apoptosis, reduced memory B cells, and immune senescence.
HEU infants have increased risk for invasive pneumococcal disease (IPD) compared with HUU children. We found increased pneumococcal density in HIV-infected mother--child pairs, regardless of the child's HIV status.
PCVs prevent IPD and intercept transmission of pneumococcus by decreasing carriage. PCVs are being introduced in India, and both CLH and HEU children need to be included in national programs, given their increased risk for pneumococcal disease.
HIV infection increases the risk of S. aureus infection. We found increased S. aureus carriage in HIV-infected mother--child pairs, regardless of the child's HIV status and higher S. aureus density in the ART naïve HIV-infected mother.
Viral respiratory infections specifically RSV cause hospitalizations and mortality in CLH and HEU children. The HEU child had frequent URIs with viral--bacterial coinfections.
The HEU child had increased carriage and exposure to respiratory pathogens including pneumococcus. Maternal HIV and ART status impact these household exposures.
Programs for prevention of mother-to-child transmission of HIV have dropped rates of HIV infection in children born to HIV-positive women. As a result, there is a growing population of children who are HIV-exposed and uninfected (HEU). This case series will aid primary care physicians and pediatricians in understanding that the HEU child also falls into the category of children who are at increased risk for infection due to perinatal exposure and continued environmental exposure. This highlights the thrust to consider HEU children in a vulnerable high-risk group by healthcare providers.
The cases reported were participant in our earlier study funded by the Indian Council of Medical Research, Government of India (letter number 5/7/463/2010-RHN dated: 15-06-2011) registered at Clinical Trial Registry-India (CTRI/2012/03/002515). This work was also funded by the Robert Austrian Research Award advisory committee 2016 (Robert Austrian Research Grant 2016).
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Indian Council of Medical Research, Government of India (letter number 5/7/463/2010-RHN dated: 15-06-2011) and Robert Austrian Research Award Advisory committee 2016 (Robert Austrian Research Grant 2016)
Conflicts of interest
There are no conflicts of interest.
| References|| |
Arya BK, Bhattacharya SD, Sutcliffe CG, Ganaie F, Bhaskar A, Bhattacharyya S, et al
. Nasopharyngeal pneumococcal colonization and impact of a single dose of 13-valent pneumococcal conjugate vaccine in Indian children with HIV and their unvaccinated parents. Pediatr Infect Dis J 2018;37:451-8.
Kuhn L, Kasonde P, Sinkala M, Kankasa C, Semrau K, Scott N, et al
. Does severity of HIV disease in HIV-infected mothers affect mortality and morbidity among their uninfected infants? Clin Infect Dis 2005;41:1654-61.
Ruperez M, Gonzalez R, Maculuve S, Quinto L, Lopez-Varela E, Augusto O, et al
. Maternal HIV infection is an important health determinant in non-HIV-infected infants. AIDS 2017;31:1545-53.
Marinda E, Humphrey JH, Iliff PJ, Mutasa K, Nathoo KJ, Piwoz EG, et al
. Child mortality according to maternal and infant HIV status in Zimbabwe. Pediatr Infect Dis J. 2007;26:519-26.
Evans C, Humphrey JH, Ntozini R, Prendergast AJ. HIV-Exposed uninfected infants in Zimbabwe: Insights into health outcomes in the pre-antiretroviral therapy era. Front Immunol 2016;7:190.
Slogrove AL, Frigati L, Gray DM. Maternal HIV and paediatric lung health. Paediatr Respir Rev 2017;21:47-53.
Afran L, Garcia Knight M, Nduati E, Urban BC, Heyderman RS, Rowland-Jones SL. HIV-exposed uninfected children: A growing population with a vulnerable immune system? Clin Exp Immunol 2014;176:11-22.