Prevalence and route of transmission of undiagnosed human immunodeficiency virus infection among children using provider-initiated testing and counselling strategy in Ido-Ekiti, Nigeria: a cross-sectional study

Introduction Ninety-one percent of global Human Immunodeficiency Virus (HIV) infection in children occurs in sub-Saharan Africa. Provider Initiated Testing and Counselling (PITC) Strategy is a means of reducing missed opportunities for HIV exposed or infected children. The present study determined the prevalence of HIV infection using PITC Strategy among children seen at the Paediatric Emergency Unit of Federal Medical Centre (FMC), Ido-Ekiti, and the possible route of transmission. Methods Cross-sectional study on prevalence of HIV infection using PITC model. 530 new patients whose HIV serostatus were unknown and aged 15 years or below were recruited consecutively and offered HIV testing. Serial algorithm testing for HIV infection using Determine HIV-1/2 and Uni-Gold rapid test kits was adopted. Seropositive patients younger than eighteen months had HIV Deoxyribonucleic Acid Polymerase Chain Reaction (HIV DNA PCR) test for confirmation. Results Twenty-four (4.5%) of the 530 patients were confirmed to have HIV infection; of whom 19 (79.2%) were less than 18 months of old; with age range of 5 to 156 months. Fifteen (62.5%) of the infected children were females; likewise, the gender specific infection rate was higher (%) among the females compared with (%) among the males. Two of the HIV infected children’s mothers were late, while the remaining 22 mothers (%) were HIV seropositive. Mother-to-child-transmission was the most likely route of transmission in the children. Conclusion PITC strategy is vital to the early diagnosis and effective control of HIV infection in children. However, this cannot be totally effective if PMTCT is not optimized.


Introduction
HIV counselling and testing (HCT) is a key intervention for HIV prevention and a critical entry point into life-sustaining treatment and care programme for those infected with the virus [1]. Knowledge of HIV status is critical to expanding access to timely HIV treatment, care and support that offers PLWHA an opportunity to receive information and tools to prevent HIV transmission to others.
Furthermore, HCT has been noted to have the potential to encourage openness, hence contributing to the reduction of fear and stigma in society [2]. Health facilities represent a key point of contact with people infected with HIV. Evidence from both industrialized and resource-constrained settings suggests that many opportunities to diagnose and counsel individuals at health facilities exist [3,4]. In Australia, a review of records at a Canberra Sexual Health Centre showed that more than half of HIV infected patients with delayed diagnosis had earlier been in health facilities especially the emergency unit, and almost all of these individuals had at least one risk factor that should have prompted healthcare providers to test and counsel for HIV infection [3]. A study in Uganda showed that about half of adult who were offered HIV testing at a hospital were subsequently found to be HIV infected and 83% were unaware of their HIV status, even though 88% had been to a health unit in the previous six months [4]. Concerned by persistent late diagnoses of HIV infection and a high proportion of people with HIV who are unaware of their HIV status, WHO and UNAIDS in 2007 issued a guidance on PITC for health facilities. The PITC strategy refers to HIV testing and counselling which is initiated by healthcare providers to persons attending healthcare facilities as a standard component of medical care provided to the patient, regardless of whether the patient shows sign and symptoms of HIV infection or not [5]. Walensky et al. [6] in a prospective study conducted in three hospital-associated urgent care centres and one emergency department in Massachusetts got a prevalence of 2.0% of undiagnosed HIV infection using PITC as against 1.9% using self-referral testing. A prospective study by Basset et al. [7] in an out-patient department in South Africa showed that routine HIV testing leads to significantly higher rates of detection of HIV infection. The policy statement on HIV Testing published by UNAIDS and WHO recommends that HIV testing and counselling be offered to all children seen in paediatric health services in generalized epidemic settings especially in acute care settings like emergency units [5]. It is hoped that children with HIV infection will be picked early thereby facilitating linkage to treatment programme. Studies using the PITC Strategy in Paediatric Units in Nigeria are few [8] presented in the PEU with any illness. The patients were recruited after signing or thumb-printing an informed consent form by the parents/caregivers. The assent of the patients who were seven years and older was sought by explaining the purpose of the study and details of the sample collection to them in a manner they would understand. Patients with documented HIV status at presentation were excluded from the study. Each patient was recruited once until the desired sample size was attained.
Sample size determination: the minimum sample size required for the study was determined using the formula: [9]. P = 0.5 (no similar study had been done in the region); d = 0.05. The estimated minimum sample size was 385. However, a total of five hundred and thirty patients were however tested. Data collection: caregivers and patients were given HIV pre-test counselling using WHO guideline on PITC with the choice of "opting out" [5]. Counselling cards for paediatric HIV disclosure adopted by Paediatric AIDS Treatment for Africa were used to obtain assent from children aged seven years and above. Pre-test and post-test information was provided in the individual sessions. An intervieweradministered questionnaire designed for the study was used to record information from each caregiver. The socio-economic classification as described by Oyedeji [10] was adopted for the present study to determine the socio-economic status of each patient. and support programme at the hospital for full evaluation and treatment as recommended by the National Guidelines for the treatment of Paediatric HIV infection in Nigeria [12]. while statistical test was done using Chi-square (χ 2 ) test. Statistical significance was set at p-value less than 0.05.
Ethical consideration: Institutional Ethical Approval was obtained from the Ethics and Research Committee of FMC, Ido-Ekiti. A written informed consent form detailing the study purpose, benefit, and possible risks to participants and their caregivers was duly signed by each caregiver. In addition, assent was obtained from children aged seven years and above who were in stable clinical condition.

Results
A total of 530 patients consisting of 296 (55.8%) males and 234 (44.2%) females participated in the study. The ages of the patients ranged between one day and 180 months, with a median age of 14 months. More than half (59.8%) of their caregivers were in social class III (Table 1) . Among the children that tested positive for HIV, more than half (62.5%) were females, likewise more than half (58.3%) were less than 12 months old. Majority of them had caregivers in social class III while none had caregivers in social class V ( Table 2). Table 3 shows variations in the prevalence of undiagnosed HIV infection among the study participants with socio-demographic characteristics. The prevalence was twice as high (6.4%), among the females compared with (3.0%) among the males Likewise, it was highest among those < 24 months of age being 6.6% and 7.2% in those < 12 months and those aged 12 -< 24 months respectively.
Children whose parents were in social class III had the highest prevalence while it was least among those in social class V. None of these variations was statistically significant. There was a statistically

Discussion
The prevalence of HIV infection has been shown to vary with locality and population subgroups. The prevalence of undiagnosed HIV infection among new patients in the present study using PITC Strategy was 4.5%. This was close to the overall national prevalence of 4.1% which also employed PITC Strategy though in a different clinical setting [13]. It was however higher than the prevalence rate of 1.4% documented for Ekiti State [13] where the present study was conducted. This may be due to the fact that the HIV prevalence rate in the present study was obtained in a hospital-based study conducted in patients who were ill compared with the otherwise healthy pregnant women attending antenatal clinics in Ekiti State [13]. Earlier reports on prevalence rate of HIV infection from Africa had shown higher figures than the finding from present study [14,15]. Most of the studies had employed the use of clinically directed criteria for screening for HIV infection which might have contributed to the high prevalence rates reported. In 1996, Lucas et al. [15] reported a seroprevalence rate of 20% among Ivorian patients obtained from a necropsy report. That was a much higher Uganda has a high national prevalence of HIV infection [16].

The prevalence rates of paediatric HIV infection in earlier reports from
Nigeria were also higher than the prevalence rate in the present study. Akpede et al. [17] in 1997 reported a prevalence of 8.6% among patients on hospital admission in the North-eastern Nigeria.
Likewise, Emodi et al. [18] in 1998 reported a prevalence of 20% from Enugu, Ojukwu and Ogbu [19] reported prevalence of 13.7% from Abakaliki while Adejuyigbe et al. [20] reported a prevalence of probably adequate in patients older than nine months. This needs to be confirmed in a larger number of patients. Oniyangi et al. [21] observed a prevalence of 5.7% among paediatric patients admitted into the National hospital in Abuja. This was slightly lower than the prevalence amongst the patients who needed to be admitted in the present study. Difference in methodology may partly be responsible for the difference in the finding. The observed difference may also be due to the fact that screening was done based on clinical criteria as established by WHO [22] in their study while all patients were screened for HIV infection using laboratory test in addition in the present study. The finding in the series by Angyo et al. [23] however contrast sharply with the finding in the present study. They found a very low prevalence rate of 1.5% among all patients on hospital admission. This may be due to the fact that their study was retrospective; and only patients diagnosed with AIDS were screened thus some asymptomatic patients may have been missed. The PITC Strategy was employed recently to study the prevalence of HIV infection in paediatric clinical settings [16,24,25]. Using PITC Strategy, Kankasa et al. [25] found a prevalence of 29.2% among patients on hospital admission in Zambia, Wanyenze et al. [16] found a prevalence of 15% among similar patients in Uganda while Rogerson et al. [25] reported a prevalence of 18.9% among Malawian patients on hospital admission. These were all prospective studies.
These were much higher than the prevalence rate of 6.6% amongst patients who were admitted into the hospital in the present study.
The observed higher prevalence rates may be a reflection of the higher prevalence of National HIV infection in these countries compared to Nigeria. Previous reports from Nigeria by Ogunbosi et al. [8] in Ibadan, Ejiofor et al. [26] in Awka and Olatunji et al. [27] in Lagos, gave prevalence rates of 10%, 5.8% and 4.52% respectively.
The HIV prevalence rate by Ogunbosi et al. [8] was higher than the finding from the present study. This may be due to the fact that all patients that presented in the hospital, including those referred with known HIV status during their study period were included. Moreover, Oyo State is known to have a higher HIV seroprevalence rate compared to Ekiti State. Though the study by Olatunji et al. [27] from Lagos was restricted to paediatric patients with haemoglobinopathy, their finding was only slightly lower than findings in the present study.
Ejiofor et al. [26] from Awka also screened all patients presenting in their health facility during the period of their study.
The differences between the prevalence rates in the previous reports and findings in the present study may have also been influenced by the documented HIV prevalence in pregnant women attending antenatal care settings in the various locations since studies have shown that a higher proportion of paediatric HIV infection is acquired through MTCT. The prevalence of HIV infection using PITC Strategy as compared with clinical criteria based-screening tends to be lower because relatively low risk populations are being screened. The role of gender as a risk factor for MTCT of HIV is not clear [18]. The male to female sex ratio was 1:1.7 among patients with HIV infection in the present study as compared with 1.3:1 for the overall study population. Although the difference was not statistically significant. It is consistent with the findings from studies by Adejuyigbe et al., [20] Oniyangi et al. [21] and Ogunbosi et al. [8] which all reported slight female preponderance. This might suggest that the female might be at higher risk of acquiring the infection, even at this early age.
However, studies from other parts of Africa have however reported a slight male preponderance [18,28]. The study population in Adejuyigbe, Oniyangi, and Ogunbosi studies were 3 days to 17 years, 6 weeks to 9 years, 0 to 15 years respectively. Children with HIV infection develop the disease manifestations early in life with more rapid course than adults. In the present study, over 95% of the patients with HIV/AIDS were five years and below with 20 (83.3%) being aged 24 months and below. Consistent with the age distribution of the HIV infected children found in our study, are the findings in the study by Spira et al. [29] among patients with HIV infection in Rwanda and Emodi et al. [18] also who reported that all patients with vertical transmission were found to be symptomatic by the age of two years in keeping with the rapid disease progression in patients without early diagnosis and initiation of HAART [18]. This is also supported by the age distribution of the HIV infected children; majority (83.3%) of whom were less than two years old.

Though other risk factors for HIV infection such as blood transfusion
and intramuscular injection were present in some of the infected and non-infected children, they were not significantly associated with the HIV status of the children. However, gene mapping is needed to ascertain whether it is the same virus seen in the children that is the same in their mothers because they were not followed from birth.
Earlier report by Emodi et al. [18] in 1998 indicated that a lower proportion (30%) of HIV infection was due to MTCT. This may have been due to a relatively higher blood transfusion rate of 68% found in their series and the fact that their study was undertaken when routine screening for HIV in donor blood was not widely available.

Authors' contributions
All authors read and approved the final version of this manuscript and equally contributed to its content. Table 1: socio-demographic characteristics of study participants