Case Discovery

Refugee families undergo voluntary health screening after arrival. In South Australia, screening usually is conducted by the Migrant Health Unit of the South Australian Department of Health but sometimes by another health unit. Children in whom BBV infection is diagnosed are referred to the Women’s and Children’s Hospital (WCH) Infectious Diseases Clinic for assessment and management. Some children are not screened on arrival, and undiagnosed BBV infections may be discovered later.

Iatrogenic BBV Infection

BBV infection acquired through injection of blood or blood products and for which vertical (mother-to-child) infection (including breast milk and surrogate breast-feeding) was ruled out by serologic testing of the mother and by history of sexual abuse and evidence of tattooing, piercing, and scarification. Iatrogenic infection, a form of horizontal transmission, usually involves mediation through injection of the BBV by a third party who might or might not be infected with the virus(es) in question. For this study, I defined an iatrogenic BBV infection according to all of the following criteria: BBV infection in a refugee child <18 years of age who was seen at the WCH Infectious Diseases Clinic during 2008–2010, who had been exposed to medical hollow-bore needles and blood products, who had acquired a BBV infection that was absent in his/her mother, and who had not been breast-fed by a surrogate or sexually abused but for whom other modes of horizontal infection could not be completely ruled out.

Search Methods and Patients

Internet searches of databases, including PubMed and Google Scholar, were performed to obtain peer-reviewed and other journal articles by using the following search terms: iatrogenic blood-borne virus infection, refugee children, blood-borne viral infections in war and transition zones, HIV, HBV, HCV. In addition, case reports of 4 refugee children seen in the WCH pediatric infectious diseases clinic during January 2008–December 2010 (Table) are summarized to illustrate the insidious nature of BBV infection. These case-patients, included here with parental written consent, were victims of their country’s chaotic or absent infection control practices consequent to war and political strife.

Case-patient 1

An 8-year-old girl was brought for treatment in early 2010. She was born vaginally in a hospital in Uzbekistan after a full-term normal pregnancy. There were no neonatal concerns. At 18 months of age, severe hematemesis developed. Blood loss required admission to a clinic in Andijan and transfusions of donated plasma and of blood donated by her father. At 7 years of age, she underwent a tonsillectomy in the same clinic. She had no illness typical of HIV seroconversion. Her mother was hepatitis B surface antigen (HBsAg) positive and HIV negative. The girl’s 2 younger siblings were BBV negative but anti-HBs positive. As part of migrant health screening on arrival in Australia in 2009, family members underwent serologic tests for HIV, HBV, and HCV. The girl was anti-HIV-1 and HBsAg positive. Her HIV load was 1,010 HIV RNA copies/mL, and HBV DNA was not detectable (<20 IU/mL) (HBeAg and anti-HBe negative) in 2009. Her father was negative for BBV markers. Her CD4 count was 260 cells/μL (19%), indicating severe immunosuppression. Examination was largely unremarkable except for severe dental caries and an ulcer on the lower gums (PCR positive for herpes simplex type 1). She began antiretroviral therapy soon after diagnosis and has responded well.

Case-patient 2

On arrival to Australia in 2010, a 9-year-old boy was discovered to be anti-HIV-1 positive on arrival. Both parents tested negative for anti-HIV-1 and anti-HCV. Through an interpreter, it was established that he had exposure to medical needles in the hospital. In 2004, he had undergone an appendectomy at the same Andijan clinic mentioned above; in summer 2008, he was admitted with “hepatitis” (presumably hepatitis A; see case-patient 3 below) to an Andijan hospital, where he received several injections (possibly vitamin K) by medical and nursing staff, but as far as is known, received no blood products and had no seroconverting-like illness. He had been asymptomatic. His prenatal history was unremarkable; he was born at term by normal vaginal delivery. He was vaccinated in Uzbekistan but to an unknown extent. He looked reasonably well. There was no lymphadenopathy. He had severe dental caries. He began antiretroviral therapy soon after his HIV-1 infection was diagnosed and has responded well.

Case-patient 3

This child, the younger sibling of case-patient 2, arrived in Australia with his family in 2010 when he was 5 years 9 months of age. At arrival screening, he was anti-HIV-1 negative and anti-HCV positive. He had attended the clinic in Andijan in November 2007 for “management” of jaundice, presumably associated with hepatitis A infection acquired from his sibling (case-patient 2), who had contracted hepatitis A and received the described treatment ≈40 days before case-patient 3 received his. Case-patient 3 was in the Andijan clinic for 10 days and received daily injections (the nature of which is unknown)—presumably the source of the HCV infection. When first seen at WCH on referral, he was asymptomatic. There were no abnormal physical findings. He was repeatedly anti-HCV positive and HCV RNA negative, indicating resolved infection.

Case-patient 4

This boy was born in Andijan in 2002. Immigration serology screening was not performed. He was first seen at WCH as a refugee in 2008 at 6 years of age after his general practitioner found him to be anti-HCV positive (anti-HIV-1 and HBsAg testing was not performed at the time). His mother was anti-HCV negative. He was born at 38 weeks’ gestation and had some neonatal problems for which he received multiple intravenous injections and blood transfusion(s) in an Andijan hospital. His 2 younger siblings were anti-HCV negative. Examination findings were normal except for serious dental caries requiring extractions. His liver function showed slightly elevated alanine aminotransferase (50 U/L [reference value 5–45 U/L]). Initially, nonquantitative HCV RNA was detectable in his peripheral blood, and in early 2011, his viral load was 623 IU/mL, at which time his liver function was entirely normal. In 2012, because of rising alanine aminotransferase (57 U/L) and increasing viral load (206,000 IU/mL), he was referred to a pediatric gastroenterologist, who noticed that anti-HIV and HBsAg/antibody tests had never been performed; results were positive for anti-HIV-1 (HBsAg and anti-HBs negative). The patient’s viral load was 18,300 RNA copies/mL. His CD4 count was 810 cells/μL (27%). Examination indicated no abnormality. His siblings and parents are anti-HIV negative.

Contaminated Injections in Health Care Settings

According to the US Agency for International Development, “consecutive wars have made it nearly impossible to conduct effective and sustainable HIV prevention activities” (19). The World Health Organization estimated that 17%–19% of injections performed in sub-Saharan Africa during 2000 were administered unsafely (20). Simonsen et al. reviewed injection practices in the developing world with disturbing findings (21).

Unsafe Injections and Blood Transfusions

The pandemic of non-A, non-B hepatitis (now attributed to HCV infection) emerged in the second half of the 20th century. Almost certainly it was triggered and fed iatrogenically by the increasing use of injections and blood transfusion. In industrialized countries, the introduction of anti-HCV screening for blood donors sharply decreased the incidence of iatrogenic hepatitis C, but HCV continues to spread in developing countries, where the virus is still transmitted through unscreened blood transfusions and nonsterile injections (33). Even in countries without conflict, failure to protect the blood supply still can occur, In western India, 23 children with thalassemia were reported as being positive for HIV infection after receiving blood transfusions during January–August 2011 (34).

Surrogate Breast-feeding and Feeding with Expressed Milk

In 2004, Shisana et al. (35) assessed blood and breast-milk exposures in children recruited from primary health clinics in the Free State province of South Africa and tested the children and their biological mothers for HIV infection. HIV positivity in children of HIV-negative mothers was associated with dental injections, surrogate breast-feeding, and feeding with expressed milk from a hospital milk room.

Other Possibilities

No data exist on sharing of contaminated equipment during self-injection in children and adolescents in countries of high BBV prevalence (36). Also, tattoos, skin piercing, and scarification are common in Africa and are detectable on examination.

Horizontal Infection Not Otherwise Specified

Information about modes of transmission in HIV-infected African children who have HIV-uninfected mothers is generally lacking. Since 1984, horizontally acquired HIV infection in African children who have HIV-negative mothers has been reported from 13 sub-Saharan countries (37). Injections related to health care provision or dental surgery (especially by informal providers) were more common in infected children, suggesting that horizontal HIV transmission through blood exposures is common in some sub-Saharan African countries.

In a 2005 serosurvey, Rehle et al. (38) estimated that the annual incidence of HIV infection was 0.5% in South African children 2–14 years of age. HIV infection in children who have HIV-negative mothers provided an estimate of horizontal HIV transmission. Medical injections, blood transfusion, and hospitalization almost certainly play a role; however, little is known about the extent and modes of horizontal HIV transmission in African children. Other contributors to the spread of BBVs include prostitution and rape in war; BBV-positive persons provide a link in the chain of infection that may lead to iatrogenesis.