| Abstract|| |
Background: The burden of mother-to-child transmission (MTCT) of HIV remains a major challenge in Nigeria, the country ranks highest globally. About 10% of global HIV-infected individuals live in Nigeria, of which 58% are women. The study analyzed risk and cofactors of MTCT in healthcare centers of Akure, Ondo State, Nigeria, between November 2014 and April 2016. Methods: A total of 240 pregnant women aged 19–43 years were recruited for the study, 114 HIV-seropositive mean age 31.81 years and 126 HIV-seronegative mean age 29.05 years as controls. High vaginal sawbs, breast milk, oropharynx, and neonates' nares were collected using sterile cotton-tipped applicator and introducing each into thioglycollate fluid medium for growth. Bacterial isolates were characterized by the standard microbiological methods and API kits. HIV serostatus of each participant was determined by HIV-1/2 strip and confirmed by Abbott enzyme-linked immunosorbent assay procedure. Sexually transmitted infections were detected by the enzyme immunoassays using commercial kits. Results: A total of 2,148 bacterial isolates were recovered from both cohorts (911 from HIV-seropositive, 864 HIV-seronegative, and 373 from neonates' nares). Predominant pathogens recovered were Staphylococcus aureus, Pseudomonas aeruginosa, and diverse corynebacteria as commensals. Coinfection of HIV with other sexually transmitted diseases (STDs) was prominent. About 92.1% of patients received combination ART. Neonates mortality rate was 10.5 and 7.8% mothers were potential transmitters. Spontaneous vaginal delivery accounted 91.7% deliveries. Conclusion: Incidence of STDs among HIV-seropositive was 77.5 and 22.5% for HIV-seronegative. Incidence of spontaneous vaginal delivery was 91.7% in HIV-seropositive women and 10.5% mortality rate recorded for neonates and 7.8% transmission for mothers posed high risk of MTCT, which is epidemiological significant.
Keywords: ARVs, breast milk, microbial agents, MTCT, oropharynx, STDs, vagina
|How to cite this article:|
Ebhodaghe BI, Ako-Nai KA, Aderoba AK. Evaluation of risk factors in MTCT among HIV-seropositive pregnant women in selected centers in Akure, South Western Nigeria. Ann Trop Med Public Health 2017;10:165-81
|How to cite this URL:|
Ebhodaghe BI, Ako-Nai KA, Aderoba AK. Evaluation of risk factors in MTCT among HIV-seropositive pregnant women in selected centers in Akure, South Western Nigeria. Ann Trop Med Public Health [serial online] 2017 [cited 2020 Apr 1];10:165-81. Available from: http://www.atmph.org/text.asp?2017/10/1/165/205567
| Introduction|| |
Mother-to-child transmission (MTCT) of the human immunodeficiency virus (HIV/AIDS) is a major healthcare challenge in Nigeria, as the country ranks highest on the globe with children acquiring HIV/AIDS. In 2012, more than 69,000 Nigerian children acquired the disease. This information on children acquisition of HIV/AIDS in Nigeria has led to a rise in the total number of children living with HIV in the country to an unprecedented 440,000. HIV infection in pregnancy has become the most common medical complication in women in some countries in sub-Saharan Africa, with 70% from heterosexual contact and more than 90% from MTCT. MTCT of HIV ranges from 15% to 40% in the absence of antiretroviral treatment and vary across countries. The HIV/AIDS epidemic intersects with the problem of maternal mortality in many circumstances. Globally, it is estimated that about 34 million people live with HIV. Nigeria alone accounts for 10% of the global population with 3.5 million Nigerians living with HIV/AIDS. About a half of the 34 million people living with HIV on the globe are women in their reproductive years. HIV infection rates in pregnant women range from less than 1% to more than 40% in different countries. Worldwide, Nigeria has the second highest number of new infections reported each year, and an estimated 3.7% of the population are living with HIV/AIDS.,, The country's prevalence among young women aged 35–39 years has been estimated to be three times higher than among men of the same age and females constitute 58% (about 1.72 million) of persons living with HIV. Reports across the globe show, more than 2 million HIV-infected women are pregnant each year, more than 90% of them in developing countries of sub-Saharan Africa, although close to 600,000 women die each year from complications of pregnancy and childbirth, the majority of them also are in resource-constrained settings. MTCT can occur in utero, during delivery and breastfeeding. The propensity of female vulnerability to HIV/AIDS acquisition can be biological, cultural, and social. Breastfeeding is responsible for a high proportion of MTCT in developing countries, where studies show 30% or more of perinatal HIV infections occur through breast milk. Dunn et al. meta-analysis reported risk of transmission through breastfeeding to be between 7 and 22%, equivalent to a doubling of transmission rates. Van de Pere et al. findings showed the risk of breast milk transmission may also depend upon other factors, such as maternal disease stage, breast abscesses, mastitis, nipple cracks, maternal vitamin A, and oral thrush in the child. In addition, a Zimbabwe study showed 31% of breastfeeding mothers of HIV-1-infected children had active nipple disease. Breast milk has also been shown to contain both cell associated and free virus, the amount of which may be related to the immune suppression of the mother and vitamin A levels. Studies have shown that in the absence of antiretroviral therapy, only 65% of HIV-infected children survive until their first birthday and less than half will reach 2 years of age. Similarly, other investigators have associated infection with lack of immunoglobulins particularly IgM and IgA in breast milk., It has also been demonstrated that the vulva and vaginal inflammation or ulceration may facilitate entry of the virus. Sexually transmitted diseases (STDs) are reported to be common in many African countries, where HIV prevalence is also high, thus predisposing women to HIV and MTCT. Inadequately treated or “silent” diseases has also been implicated to be a major factor in facilitating HIV infection and chlamydial infections and other sexually transmitted diseases may also act as cofactors for HIV transmission in patients. Furthermore, studies of syphilis rates as high as 30% have been described in antenatal women and 4.2% of women in a population-based study in Tanzania reported a history of genital ulceration was established as a cofactor for HIV acquisition in that region and thus facilitated MTCT. Similarly, a Zimbabwe study reported women with a history of genital ulceration and pelvic inflammatory disease were six times more likely to be HIV-positive than normal individuals. It has also been reported that improved STDs treatment in a randomized controlled trial in Tanzania reduced the rate of new HIV infections underscoring the role of STDs in HIV infections and MTCT in general. However, more studies are required in Nigeria in understanding risk factors associated with MTCT, particularly in resource constrained centers, hence our study that evaluated the risk factors of MTCT among HIV-seropositive pregnant women that attended antenatal and postnatal clinics of selected healthcare centers. High vaginal swabs (HVSs), breast milk of lactating mothers, swabs from oropharynx of mothers, and the anterior nares of neonates were cultured on appropriate blood agar, selective and differential microbiologic media for analyses. HIV-seronegative pregnant mothers were equally screened to serve as controls. To our knowledge, we are not aware of such prospective study was ever done in this environment. The findings of our study we believe will provide useful information both clinically and research wise to better understand and manage HIV-seropositive patients and reduce MTCT. It will also provide therapeutic experience to clinicians in treating HIV-seronegative group in reducing pathogenesis among microbial strains in the event of an epidemic. It will also provide useful database research findings, which hitherto have not been available at these centers, thus strengthening the research capacity in this region.
| Materials and Methods|| |
All the study participants, including controls, were pregnant women who attended the ante-natal clinics of the selected study centers. Four centers were used for this study in two local government areas (LGA) in Ondo State, such as State Specialist Hospital and Mother and Child Hospital Akure South LGA located at 7 15′0″N 5 11′42″E/7.25000 N latitude 5.19500°E longitude, which is the largest city and capital of Ondo State, South Western Nigeria. The other centers were General Hospital Igbara-oke and Basic Health Center Igbara-oke in Ifedore, LGA in Ondo State, at a distance of 152 km2 from Akure. Information relating to each participant was obtained through verbal interview, questionnaire responses, and case files managed by the attending physicians.
Criteria for study inclusion
Enrolment at the ante-natal clinic of the hospital and strict compliance by HIV-seropositive patients participating in highly active antiretroviral therapy (HAART) in accordance with the national guidelines on HIV/PTMTC (prevention of transmission from mother-to-child) policy was the inclusion patients' criteria. Participants were also encouraged to keep all physician appointments throughout the study. All patients who consented were not restricted by age and were registered for the study. HIV status of each patient was determined through blood screening at the HIV center of the hospital and was also a requirement for inclusion in the study. The screening was done at the onset of the study during which patients were at their third trimester of pregnancy.
Those patients who did not fall into the above categories, that is patients who did not comply with revisit and those who declined involvement in the study were not included.
HIV screening among cohort
[5A] mL volume of blood was collected in a sterile vacutte EDTA tubes K3 and in sterile 38 × 0.8 mm needles from each participant. A small aliquot was applied onto the HIV-1/2 strip (Determine Test, Alére, London, England, UK) for the preliminary determination of HIV serostatus. Confirmatory test for HIV infection was performed using the Abbott ELISA procedure (Abbott Laboratories, Chicago, IL, USA).
Whole blood of each patient was used for CD4+ T-cell assay; the value was documented as baseline CD4+ T-cell percentage or count/µL. This was repeated at 3 and 6 months later. The CD4+ T-cell count was done using flow cytometry (CyFlow SL-3 Code No. CY-S-1023, Partec GmbH, otto-Hahn-Strasse 32-48161, Muenster, Germany), the EDTA-treated whole blood was analyzed within 6 hours of collection following manufacturers protocol (Partec GmbH, 2006®).
Whole blood collected for immunologic assessment was used for the virologic assessment to avoid multiple venipuncture. Serum was separated from whole blood by centrifuging at 3,000 revolution per minute for 5 min at room temperature within 6 hours of blood collection, aliquoted, stored in a sterile polypropylene tube and frozen at −70°C until processing for viral load assay was conducted. The viral load (plasma HIV RNA copies), which quantifies the viral burden of HIV in the blood (WHO, 2006) was assayed for only in HIV-seropositive patients. The COBAS® AmpliPrep TaqMan HIV-1 Qual test version 3.2 series 3.3 Kit was employed for the assay following manufacturers' procedure.
Collection of high vaginal swabs
Isolation and identification of bacterial isolates
A sample of HVS was collected from the posterior fornix from each pregnant patient by the attending physician using sterile bivalve speculum (Changzhou Huankang Medical Devices Co. Ltd., Changzhou City, Jiangsu Province, China) and sterile cotton-tipped applicator (Evepon, Industrial Ltd., Onitsha, Anambra State, Nigeria) into freshly prepared sterile thioglycollate medium and incubated at 37 °C for 24 h for growth. After growth was observed, a loopful of the sample was streaked initially with the aid of heat-flamed standard aluminum wire loop (delivering 0.001 mL on to freshly prepared agar plates – blood agar, proteose peptone agar, and mannitol salt agar [MSA]). Thereafter, the plates were incubated aerobically at 37°C for 24 h and anaerobically in AnaeroPack jar 2.5 L, order no. 50-25, product of Mitsubishi Gas Chemical Company Co., Inc., 5-2 Marunouchi 2-chome, Chiyoda, Tokyo, Japan (all samples were analyzed within 24 h of collection) for growth. Only plates on which colonies appeared were examined. Each distinct colony appearing on agar plates was picked and further studied. Each colony was classified based on cultural and morphological characteristics such as size, elevation, opacity, and color on media plates. Initial Gram's stain was prepared for each colony and further identification of each colony was based on their reaction on conventional enriched, selective, and differential media. Colonies in clusters resembling staphylococci were inoculated onto MSA and those colonies that fermented mannitol on MSA were presumptively identified as Staphylococcus aureus and confirmed as such by the coagulase slide and tube agglutination tests with pooled human plasma. Further, confirmatory test was done on DNase and RNase agar. Coagulase negative staphylococci (CONS) were identified using sugar fermentation test. Coagulase, catalase tests, growth on bile aesculine agar (Oxoid Ltd., Basingstoke, Hampshire, England, UK) and sensitivity to Taxo A disc (0.04 units of bacitracin) and Taxo P disc (5 µg) ethylhydrocupreine hydrochloride (optochin; BD Diagnostics, Difco Laboratories, Detriot, MI, USA) were also employed for identification of streptococci and enterococci. Furthermore, isolates resembling Neisseria More Details species were cultured on protease peptone agar (Difco Laboratories) supplemented with serum and determined by sugar fermentation test including glucose, maltose, sucrose, and lactose. Only Gram-negative diplococci isolates with bean shape colonies and positive for glucose fermentation were confirmed Neisseria gonorrhoeae More Details. Colonies that were Gram-negative rods were identified as lactose or non-lactose fermenters using eosin methylene blue (EMB) and MacConkey agar. Further speciation of isolates were based on their activities on convectional media such as triple sugar iron agar (TSI), Koser's citrate medium, sulphide indole motility agar (SIM), and urea agar (Oxoid) and according to methods described by Barrow and Feltham. Gram-positive rods that grew on conventional media were also classified as spore formers and non-spore formers. The analytical profile index (API) kits used include API 20E and API Staph (bioMéerieux, Marcy l'Etoile France).
Collection and processing of oropharyngeal samples
A sample of oropharyngeal swab was obtained from each patient by the attending physician using a sterile cotton-tipped applicator that was initially dipped in sterile saline. Each sample was then inoculated into duplicate sterile thioglycollate fluid media and separately incubated at 37°C aerobically for 24 h and in anaerobic jars for 48 h (AnaeroPack Jar 2.5 Liter, Order No. 50-25, product of Mitsubishi Gas Chemical Company Co., Inc., 5-2 Marunouchi 2-chome, Chiyoda, Tokyo, Japan). For bacterial identification, a loopful of each culture was streaked onto blood agar (BA), chocolate agar (CA), mannitol salt agar (MSA), EMB agar, sulfide indole motility agar (SIM), koser citrate agar, and triple sugar iron agar (TSI; Oxoid Ltd.). The plates were incubated aerobically and anaerobically at 37°C for 48 h. Colonies that grew on each culture medium were Gram stained and processed for biochemical identification using the API 20E and API Staph (bioMéerieux, , Marcy l'Etoile, France).
Collection and processing of breast milk samples
Breast milk sample (102 in all) was collected from each lactating mother (made up of 99 samples collected from HIV-seropositive women and only 3 sample each from HIV-seronegative mothers because of restrain by the participants). Breast milk samples were collected from HIV-seropositive mothers at three periodic intervals: first, 70 samples were collected immediately after birth (1–14 days of delivery), 18 samples were collected 180 days later, and 11 samples 270 days later. However, only three breast milk samples were collected from HIV-seronegative lactating mothers because of restraint. Criteria for collection was strict as patients were requested to clean their hands and the breasts with sterile warm water, as each sample was collected into sterile calibrated test tube by manual expression. One milliliter of each breast milk sample was inoculated into freshly prepared sterile thioglycollate medium and incubated at 37 oC for 24 h for growth. Thereafter, samples were analyzed according to method used in processing HVS.
Nasal carriage of bacterial isolates in neonates
In addition, a nasal swab from each neonate was obtained from within the first to 14 days of birth. Each swab was initially moistened with a sterile normal saline and gently introduced into the anterior nares of each neonate by careful rotation by the clinician/nurse. Such a sample was thereafter introduced into freshly prepared sterile thioglycollate medium and incubated at 37˚C for 24 h for growth. Thereafter, samples were analyzed similar to those isolates recovered from oropharynx.
Sexually transmitted infections assays
Sexually transmitted infections (STIs) among patients were detected using sera obtained from both HIV infected and HIV noninfected pregnant women using enzyme immunosorbent assay (EIA). Only clear nonhemolyzed specimens were used. Specimens were brought to room temperature after being thawed. The ELISA method was used for detection of hepatitis B virus (HBV), hepatitis C virus (HCV), human papilloma virus-6 (HPV), and herpes simplex virus type-2 (HSV-2). For HBV infection, the patient tested positive for HBV surface antigen (HBsAg). Similarly, for the detection of other antigens (HCV, HPV-6, and HSV-2), two drops of plasma each was transferred to the cassette that contained coated antigen with a disposable pipette provided in the kit by the manufacturer (ABON, Abon Biopharm [Hangzhou] Co., Ltd., Hangzhou, PR China). Thereafter, a drop of buffer was added to the cassettes and the assay was timed. VDRL (syphilis) was detected from each patient by rapid plasma reagin test. Two drops of plasma from each participant was placed on a strip that contained coated antigen of Treponema palladium. Thereafter, a drop of buffer was added to each strip and timed. The VDRL assay has limitations: sometimes the results are negative in patients with incubating syphilis, limited sensitivity during the early primary stage within the first 10 days after which lesion appears. The use of lesion-based testing and presumptive diagnosis therefore may be the only means of diagnosis.
Trichomonas vaginalis was detected by preparing a wet smear on a clean grease free slide with a drop of sterile normal saline and high vaginal fluid sample collected from the patients. Each patient presenting with T. vaginalis was initially examined for clinical symptoms of yellow discharge, abnormal vaginal odor, vulval itching, and signs of colpitis macularis (“strawberry cervix”) purulent vaginal discharge and vagina and vulvar erythema. Although sensitivity of symptom and signs are relatively low for this test, nonetheless, clinical manifestations are routinely used to identify patients for whom wet mount examination would likely have high yield. Subsequently, the wet smeared slide was viewed under the microscope bright field at ×40 objective for highly motile tiny spear-shaped flagellates with an axostyle. This was performed within 10–20 min of collection of the sample.
The presence of Chlamydia trachomatis in HVS sample was determined by EIA using cervical mucus obtained from the posterior fornix of the vaginal of each patient. Each sample was introduced into a cassette that contained coated antigen provided in the kit by the manufacturer (ABON, Abon Biopharm [Hangzhou] Co., Ltd). Buffer (reagents A and B) was introduced to the cassette and an immediate change in color to purple was observed, indicative of a positive test.
Determination of immunoglobulins in breast milk samples and sera
The breast milk and serum samples of each participant was measured for concentration of antibodies by the ELISA methods of Voller and Bidwell. In the assay, polyvinyl microtiter 96-wells obtained from (Dynatech, Immunlon TM14340, VA, USA) and coated with coating buffer was incubated at 4 ˚C overnight with dilutions of antigen made in 100×, 200×, 500×, 1000×, and 2000× concentrations. After appropriate washing with PBS-Tween buffer and the final addition of p-nitrophenyl phosphate as substrate, the specific antibodies (IgG, IgM, and sIgA ) were determined from corrected absorbance readings at 450 nm.
Statistical analysis of data
Statistical evaluation was done using Student's t-test and one-way analysis of variance with P ≤ 0.05 as the indicator of statistical significance. SPSS 2007 (SPSS Inc., Chicago, IL, USA) version 17.0 for Windows was used to perform the analyses.
| Results|| |
The results showed altogether 2148 bacterial isolates were cultured from four different sources from the participants comprising of HIV-seropositive and HIV-seronegative HVSs, breast milk, the oropharynx of both HIV-seropositive and HIV-seronegative patients and the anterior nares of neonates of HIV-seropositive patients only. In addition, 99 breast milk samples were collected from HIV-seropositive mothers and only three samples were collected from HIV-seronegative mothers.
The number of bacterial isolates recovered from HVS from both HIV-seropositive and HIV-seronegative mothers 1156/2148 = 53.8%, comprising of HVS from HIV-seropositive mothers 549/1156 = 47.49% and HIV-seronegative comprising of 607/1156 = 52.51%; breast milk samples 153/2148 = 7.1% comprising of 145/153 = 94.7% for HIV-seropositive and 8/153 = 5.2% for HIV-seronegative patients, anterior nares of neonates of HIV-seropositive mothers 373/2148 = 17.36%, oropharynx 466/2148 = 21.7% comprising of 217/466 = 46.6% for HIV-seropositive patients whereas 249/466 = 53.4% for HIV-seronegative patients.
The results also showed that the predominant organisms were Gram-positive rods (nonspore formers) consisting 839/2148 = 39% comprising of Arcanobacterium haemolyticum 216/839 = 25.7%, Corynebacterium xerosis 233/839 = 27.7%, Corynebacterium ulcerans 74/839 = 8.8%, and Corynebacterium pseudotuberculosis 57/839 = 6.7%. In addition, C. pseudodiphtheriticum constituted 38/839 = 4.5% followed by Corynebacterium jeikeium 33/839 = 3.9% and Corynebacterium diphtheriae 31/839 = 3.7%. Furthermore, Corynebacterium amycolatum only constituted 21/839 = 2.5%. Other Gram-positive rods seen included Listeria monocytogenes 62/839 = 7.4%, Gardnerella vaginalis 10/839 = 1.1%. Also recovered were Lactobacillus acidophilus 32/839 = 3.8%, Lactobacillus reuteri 5/839 = 0.5%, Lactobacillus brevis 6/839 = 0.7%, Lactobacillus salivarius 1/839 = 0.1%, Lactobacillus casei 3/839 = 0.35%, and Lactobacillus spp recovered 15/839 = 1.78%. Only 2/839 = 0.2% was Actinomyces israelii. Furthermore, the results showed staphylococci were recovered from 549/2148 = 25.6% of which S. aureus constituted 114/549 = 20.7% and the rest of which were coagulase negative staphylococci (CONS) 435/549 = 79.2%. Micrococcus isolates were also recovered from 219/2148 = 10.1% of the samples comprising of Micrococcus luteus 164/219 = 74.9%, Micrococcus lylae 43/219 = 19.6%, Micrococcus agilis and Micrococcus roseus 2.7% each. Among the Gram-negative rods, non-lactose fermenters constituted 204/2148 = 9.49% of the bacterial isolates Providencia rettgeri and P. aeruginosa both constituted 42/204 = 20.58% each, Proteus mirabilis was 25/204 = 12.25%, Serratia marcescens 21/204 = 10.29% and Proteus vulgaris and Salmonella More Details typhimurium 14/201 = 6.7% each. Chryseomonas luteola was recovered in 12/204 = 5.8% followed by Pseudomonas fluorescence 10/204 = 4.9% and Streptobacillus moniliformis 5/204 = 2.4% whereas Salmonella enteritidis 4/204 = 1.96% and Proteus penneri 0.98%. Among the lactose fermenters, 104/2148 isolates 6.55% were recovered comprising of Enterobacter aerogenes 44/140 = 31.42%, Escherichia More Details coli 42/140 = 30%, Klebsiella pneumoniae 22/140 = 15.71%, and Citrobacter freundii 13/140 = 9.2%. In addition, Enterobacter cloacae 8/140 = 5.7% and Klebsiella oxytoxa 6/140 = 4.3% and Citrobacter diversus 5/140 = 3.5%. Among the spore formers bacilli recovered in 101/2148 = 4.7% comprising Bacillus subtilis 65/101 = 64.4%, Bacillus cereus 21/101 = 21.78%, Bacillus sphaericus 9/101 = 8.9%, and Bacillus mycoides 5/101 = 4.9%.
Furthermore, 56/2148 = 2.6% of the isolates were streptococci comprising of Streptococcus pyogenes 26/56 = 46.4%, Group B streptococcus (viridians) 21/56 = 37.5%, Streptococcus pneumoniae 8/56 = 14.2%, and Streptococcus salivarius 1/56 = 1.7%, whereas enterococci 33/2148 = 1.5% made up of Enterococcus faecalis 24/33 = 72.72% and Enterococcus faecium 9/33 = 27.27% and N. gonorrhoeae 7/2148 = 0.32% from the four sources [Table 1].
|Table 1: Comparative analysis of bacterial isolates cultured from high vaginal swabs, breast milk, oropharynx of HIV-seropositive, and HIV-seronegative women and neonates anterior nares|
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[Table 2] showed the pattern of distribution of STIs among HIV-seropositive and HIV-seronegative pregnant women in selected centers [Table 2]. The results showed overall 31/62 = 50% tested positive for T. vaginalis (TV), 7/62 = 11.3% tested positive for HBV, and 5/62 = 8.0% tested positive for HSV-2 and N. gonorrhoeae each. Furthermore, 6/62 = 9.7% of the participants tested positive for HPV-6 and syphilis (VDRL) each and 2/62 = 3.2% tested positive for C. trachomatis. Using enzyme immunoassay (EIA) kits, no STIs was encountered at age ≤19 years among the HIV seropositive patients. The results however showed, three patients aged 20–25 years tested positive for STIs one of which was T. vaginalis and two other women tested positive for STIs. Eleven of these individuals tested positive for T. vaginalis, three for HBV, two for herpes simplex type 2 virus (HSV-2) whereas three individuals tested positive for syphilis and one for C. trachomatis infection. Furthermore, 32 patients aged between 32 and 37 years also tested positive for STIs, 16 of these individuals were positive for T. vaginalis, 2 had HBV infection, 1 individual had HSV-2 infection, and 5 of the women tested positive for HPV-6. Similarly, two individuals had syphilis whereas only one individual tested positive for C. trachomatis and five individuals were positive for N. gonorrhoeae.
|Table 2: Profile of sexually transmitted infections in relation to age among HIV-seropositive pregnant women|
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Finally, seven of the individuals aged 38–43 years had STIs, three tested positive for T. vaginalis, two tested positive for HBV, one each was positive for HPV-6 and syphilis (P = 0.05) [Table 2].
[Table 3] showed the pattern of distribution of STIs among HIV-seronegative pregnant women in selected centers [Table 3]. Overall, among the seronegative mothers, 18/126 = 14.2% had STIs. 4/18 = 22.2% tested positive for TV. 3/18 = 16.6% tested positive for HBV infection whereas 1/18 = 5.5% tested positive for HSV-2 virus, and 2/18 = 11.1% each tested positive for HPV-6, syphilis, and gonorrhea. However, 4/18 = 22.2% tested positive for C. trachomatis. Furthermore, among age range ≤19 years only one individual tested positive for STIs of which tested positive for HPV-6. Among five individuals aged 20–25 years, one individual tested positive each for T. vaginalis, HBV, herpes simplex type 2 virus HSV-2 and C. trachomatis. However, seven of the women aged 26–31 years, tested positive for STIs, three tested positive for T. vaginalis, one HBV, one syphilis, one had C. trachomatis, and one had N. gonorrhoeae.
|Table 3: Profile of sexually transmitted infections in relation to age among HIV-seronegative pregnant women|
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Furthermore, four women aged 32–37 years also tested positive, one each for syphilis, N. gonorrhoeae and two positive for C. trachomatis. However, one woman between age range 38 and 43 years tested positive for HBV (P = 0.002) [Table 3].
[Figure 1] showed the pattern of antenatal serum concentration of CD4+ T-cell count cells/mm3 compared to plasma load of RNA copies/mL among HIV-seropositive pregnant women. The figure compared the mean CD4+ T-cell count concentration or value in relation to age among HIV-seropositive pregnant women. [Figure 1] showed only the mean CD4+ T-cell count of each different age range, which is as follows: nine individuals in age range 20–25 years had mean CD4+ T-cell count of 427 cells/mm3, 36 individuals in age 26–31 years had mean CD4+ T-cell count as 438 cells/mm3. Similarly, among 57 individuals aged 32–37 years, mean CD4+ T-cell count was 378 cells/mm3 and of the 12 individuals with age range 38–43 years, mean CD4+ T-cell count was 475 cells/mm3. In addition, nine of the individuals aged 20–25 years, mean plasma viral load was 4313 RNA copies/mL, 36 women aged 26–31 years, mean plasma viral load was 3987 RNA copies/mL. Furthermore, 57 women aged 32–37 years, mean plasma viral load was 19 742 RNA copies/mL and 12 individuals aged 38–43 years, mean plasma viral load was 3280 RNA copies/mL [Figure 1].
|Figure 1: Pattern of antenatal concentration of CD4+ T cells/mm3 compared to plasma viral load (RNA copies/mL) among HIV-seropositive pregnant women|
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[Table 4] showed the effect of HIV-seropositivity on clinical prognosis and pregnancy outcomes in relation to age. The mean age of the 114 participants was 31.20 years, whereas the mean weight of the neonates was 3.03 kg. The mean of CD4+ T-cell count was 429 cells/mm3 and the mean of the plasma viral load was 7830.5 RNA copies/mL. Regarding the adverse pregnancy outcome among 114 participants, the data obtained from their case files revealed a total of one prematurity, seven prolonged labor, and seven still birth. Furthermore, the data also showed that one each of the mothers experienced miscarriage and postpartum death. The results of the mode of delivery among participants showed 100 (100/109 = 91.7%) had spontaneous vaginal delivery whereas 4 (4/109 = 3.5%) experienced elective caesarean sections. However, only 5 (5/109 = 4.6%) of the participants experienced emergency caesarean section deliveries. The results also showed the mean age of HIV-seropositive individuals in relation to age group. Among nine mothers, mean age was 23.44 ± 1.66 (SD), SME (0.55). Similarly, among 36 mothers aged 26–31 years, the mean age value was 28.58 ± 1.51 (SD), SME (0.26). With regards to 57 mothers, the mean age was 33.74 ± 1.56 (SD), SME (0.21). Furthermore, among 12 mothers, the age mean value at 38–43 years was 39.25 ± 1.60 (SD), SME (0.46). When CD4+ T-cell count (cells/mm3) were calculated among nine individuals within age group 20–25 years, the mean CD4+ T-cell count was 427 cells/mm3 and mean plasma viral load was 4313 RNA copies/mL whereas among 36 mothers between 26 and 32 years old, the mean CD4+ cell count was 438 cells/mm3 and mean plasma viral load 3987 RNA copies/mL whereas among 57 mothers aged 32–37 years, mean CD4+ T-cell count was 378 cells/mm3 and mean viral load was 19 742 RNA copies/mL. In contrast, among 12 mothers aged 38–43 years, the mean CD4+ T-cell count was 475 cells/mm3 whereas the mean plasma load was 3280 RNA copies/mL. With regards to mean weight of neonates, the neonates had different values because some had died during the process; therefore, the mean weight value of neonates at 20–25 years age group among eight neonates was 3.10 kg, ±1.09E1 (SD), SME 3.8, and among mothers aged 26–31 years, 18 neonates were involved and mean age was 3.12 kg, ±0.43 (SD), SME 0.15. Similarly, among women aged 32–37 years including 36 neonates, mean weight was 3.04 kg, ±0.51 (SD), SME 0.019. Finally, among mothers aged 38–43 years with eight neonates mean age was 2.87 kg, ±0.25 (SD), and SME 0.125.
|Table 4: Effects of HIV-seropositivity on clinical prognosis and pregnancy outcomes|
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With regards to adverse pregnancy outcome in relation to age group, the results showed the following, among nine mothers aged 20–25 years, none of the nine mothers suffered prematurity, prolonged labor, miscarriage, and postpartum death. However, one (1/9 = 11.1%) mothers' neonate was still born. Among 36 mothers aged 26–31 years, none of the neonate was born prematurely, still birth, and postpartum death. However, one mother suffered prolonged labor and miscarriage each (1/36 = 2.7%). Similarly, among age range 32–37 years consisting of 57 mothers, one of their neonates each suffered prematurity and postpartum death (1/56 = 1.7%), six mothers had prolonged labor of which one of the mothers had rupture of the membrane (6/56 = 10.7%), five of the neonates were still born (5/56 = 8.9%). However, none of the babies was miscarried. The results also revealed among 12 mothers aged 38-43 years, none experienced prematurity, prolonged labor, miscarriage, and postpartum death. However, one of the neonate's (1/12 = 8.3%) was still born. The results also showed that when mode of delivery was assessed, among nine mothers aged 20–25 years, eight (8/9 = 88.9%) had spontaneous vaginal deliveries but none had elective nor experienced emergency caesarean section delivery. Among 36 mothers aged 26–31, 33 (33/36 = 91.7%) had spontaneous vaginal deliveries, one had elective and emergency caesarean section delivery each (1/36 = 2.8%). Furthermore, among 57 mothers aged 32–37, 49 (49/57 = 95.9%) had spontaneous vaginal deliveries, two (3.5%) had elective caesarean section deliveries, and four (4/57 = 7.0%) had emergency caesarean section deliveries. Finally, among the 12 mothers aged 38–43, 10 (10/12 = 83.3%) experienced spontaneous vaginal deliveries one (1/12 = 8.3%) had elective caesarean section delivery and no emergency caesarean section delivery was experienced by mothers this group.
[Table 5] showed the relative antibody levels in breast milk and sera of HIV-seropositive mothers determined by ELISA methods. The results showed the mean class-specific immunoglobulin levels in breast milk among 70 HIV-seropositive mothers as follows: IgG = 0.051 ± 0.025 (0.00300), mean IgA 0.046 ± 0.022 (0.002), and IgM = 0.048 ± 0.048 (0.003) . For mean maternal sera among 97 HIV-seropositive mothers, the mean immunoglobulin levels were as follows: IgG = 0.054 ± 0.023 (0.002), IgA = 0.062 ± 0.032 (0.003), and IgM = 0.056 ± 0.024 (0.002). The P values were also as follows: IgG = 0.428, IgA and IgM was 0.002 each.
|Table 5: ELISA determination of relative antibody levels in breast milk and sera among HIV-seropositive pregnant women|
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Furthermore, [Table 6] showed the relative antibody levels in breast milk and sera of HIV-seronegative mothers determined by ELISA techniques. The results revealed the mean class-specific immunoglobulin values in breast milk among only three HIV-seronegative mothers as follows: IgG = 0.045 ± 0.031 (0.018), mean IgA levels 0.039 ± 0.0075 (0.004), and IgM = 0.036 ± 0.010 (0.006). Similarly, mean maternal sera levels were as follows: IgG = 0.052 ± 0.017 (0.002), IgA = 0.0613 ± 0.0205 (0.002), and IgM = 0.052 ± 0.014 (0.002). The P values of the immunoglobulins were as follow: IgG = 0.852, IgA = 0.167, and IgM = 0.085.
|Table 6: ELISA determination of relative antibody levels in breast milk and sera among HIV-seronegative pregnant women|
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The profile of antiretroviral efficacy among HIV-seropositive mothers regarding their CD4+ T-cell count, plasma viral load (RNA copies/mL), access, and effect on neonate survival is shown in [Table 7]. Altogether, 114 women were HIV-seropositive, of whom 105 (92.1%) were on HAART. Sixty (57.1%) of these individuals were AZT/3TC/NVP and 43 (40.9%) were on TDF/3TC/EFV, whereas only 2(1.9%) was on TDF/FTC/LIP due to WHO staging of their disease progression. However, among the four categories analyzed, A represented 60 individuals on AZT/3TC/NVP with a mean CD4+ T-cell count of 436.51 cell/mm3 and mean viral load of 11 175.4 RNA copies/mL. The result also shows nine of the patients changed their ARV therapy because there were out of stock and only one patient reacted to the drug.
|Table 7: Profile of antiretroviral efficacy among HIV-seropositive mothers regarding their CD4+ T-cell count, plasma viral load (RNA copies/mL), access and effect on neonate's survival|
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B represented 43 patients on TDF/3TC/EFV whose mean CD4+ T-cell count was 319.07 cells/mm3 and viral load 10 987 RNA copies/mL of which three changed their drugs because there were out of stock.
C represented nine patients whose mean viral load were highest ≥50,000. Five of these patients were on TDF/3TC/EFV and three on AZT/3TC/NVP and one naaive. One was on septrin and the reason for the other changing drug was due to psychosis.
D represented HIV mothers who lost their neonates during the course of the study. Their mean CD4+ T-cell count was 477.6 cells/mm3, viral load 8918.5 RNA copies/mL of whom eight of the mothers were on AZT/3TC/NVP and four on TDF/3TC/EFV. Five of these women changed their drugs, four of whom was as a result of been out of stock, and one reacted to the drug. All their babies died within 12 months.
| Discussion|| |
The study evaluated the risk factors of mother-to-child transmission in the vagina, breast milk of lactating mothers, oropharynx, and nares of selected neonates. Altogether, 2148 bacterial isolates were recovered from the four sources. The number of bacterial isolates recovered from HVS from both HIV-seropositive and HIV-seronegative mothers 1156/2148 = (53.8%), comprising of HVS from HIV-seropositive mothers 549/1156 = (47.49%) and seronegative comprising of 607/1156 = 52.51%; breast milk samples 153/2148 = 7.1% comprising of 145/153 = 94.7% for HIV-seropositive and 8/153 = 5.2% for HIV-seronegative patients, anterior nares of neonates of HIV-seropositive mothers 373/2148 = 17.36%, oropharynx 466/2148 = 21.7% comprising of 217/466 = 46.6% for HIV-seropositive patients whereas 249/466 = 53.4% for HIV-seronegative patients. A total of 1156 bacterial isolates was recovered from 240 women averaging 4.8 bacterial isolates per patient whereas bacterial isolates recovered from breast milk samples was 153/73 averaging 2.09 bacterial isolate per patient. In addition, bacterial isolates recovered from the oropharynx was 466/240 = 1.94 bacterial isolate per patient. Our results revealed the predominant isolates were recovered from HVS (53.8%) followed by the oropharynx 466/2148 = (21.69%), the anterior nares of neonates (17.36%). Similarly, bacterial isolates recovered from breast milk samples constituted (7.1%).
Furthermore, bacterial isolates recovered from HIV-seropositive and HIV-seronegative patients were compared in relation to their pathogenic potential in the four sources (HVS, breast milk, oropharynx, and anterior nares of neonates). Our results compared the predominant pathogens in the four sources. Thirty-two S. aureus isolates were recovered from HIV-seropositive individuals whereas 26 S. aureus isolates were recovered from HIV-seronegative patients. In contrast, among breast milk samples analyzed, eight S. aureus was recovered compared with none in HIV-seronegative patients. However, in the oropharynx of HIV-seropositive patients, 10 S. aureus were encountered compared to 19 almost twice the number in HIV-seronegative mothers. The 19 S. aureus recovered from the anterior nares were from HIV-seropositive mothers' neonates none from HIV-seronegative neonates. The pathogenicity of the isolates are derived from elaboration of enzymes, toxins, and resistant plasmid, which confer on these strains antibiotic resistance. Thirty-two S. aureus isolates were recovered from the HIV-seropositive women, whereas 26 S. aureus isolates were recovered from HVS from HIV-seronegative women. In addition, eight S. aureus isolates recovered from breast milk samples of HIV-seropositive women and none from the HIV-seronegative counterparts. Furthermore, 10 S. aureus isolates were recovered from the oropharynx of HIV-seropositive and 19 S. aureus isolates were recovered from HIV-seronegative women. This result suggests plausible vertical transmission from mother-to-child or from handlers. The incidence of nasal carriage of S. aureus was reported as 46% among infants as compared with 26% among the adults as seen in this study, suggesting that the neonates were twice as prone as their mothers to be colonized probably due to the number and types of bacteria as well as their relatively immature immune system., In addition, 19 S. aureus isolates were recovered from the anterior nares of neonates of HIV-seropositive mothers. Altogether, 42 P. aeruginosa isolates from the four sources of which HVS constituted 22/42 = 52.38%, ironically, none of P. aeruginosa isolate was seen in any of the breast milk samples, 11/42 = 26.19% was recovered from nares of neonates whereas 9/42 = 21.4% was cultured from the oropharynx emphasizing the dominance of pathogens among isolates recovered from HVS probably due to the microbiota, pregnancy, and hormones. Our results also revealed the predominance of Gram-positive rods among the cohorts [Table 1]. It is interesting to note the fact that the majority of the isolates were A. haemolyticum and corynebacterium isolates, which have been reported as commensals of the skin and epithelium. However, C. ulcerans and C. jeikeium have been encountered among HIV patients in some studies. The incidence of Corynebacterium jeikieum was unusually high in breast milk of these mothers. The report of the presence of this unique organism in breast milk has rarely been reported in literature in this environment but the organism has been associated with bacteremia in some immunocompromised patients. It is surprising to note that 31 C. diphtheriae were isolated from the four sources, 1/31 = 3.2% each from HVS and nares of neonates, 5/31 = 16.1% from breast milk samples, and surprisingly 24/31 = 77.4% from oropharynx. The occurrence in strikingly high numbers of C. diphtheriae in the oropharynx is of concern because the organism is known to possess potent exotoxins that can cause diphtheria. Many studies have reported the colonization of the vagina by lactobacilli, some of which act as probiotics to a healthy vagina. Our study also revealed the colonization of the vagina with lactobacilli. However, 29 L. acidophilus isolates were recovered in HVS compared with breast milk samples with five L. brevis, three each of L. reuteri, L. casei, and L. acidophilus, one L. salivarius isolate. In addition, 15 Lactobacillus spp were encountered in the oropharynx in both cohorts. Two L. reuteri and one L. brevis isolate was recovered from the anterior nares of the neonates. Our study revealed 10.3% of the bacterial isolates in breast milk of HIV-seropositive mothers were lactobacillus species, which is interesting as they are major probiotics. Our study showed L. reuteri (3/15 = 20%) was recovered from breast milk of lactating mothers. Sinkiewicz and Ljunggren reported 15% of mothers had detectable L. reuteri in their breast milk 6–32 days after delivery, which corroborates our current findings, where 20% of the lactobacillus species cultured composed of Lactobacillus reuteri, which is the first ever reported of this isolate in breast milk samples in this environment. It has also been shown that expressed breast milk may contain commensal bacteria, which could inhibit pathogenic S. aureus. This is often accomplished by competing for nutrients, host cell binding sites, and pathogen killing by producing hydrogen peroxide and bacterocin, alternatively known as bacteriotheraphy. Interestingly, none of the breast milk samples processed in our study contained Gram-negative organisms similarly reported in other studies.
The majority of pediatric transmission often occurs via MTCT. MTCT occurs through three routes, in utero, delivery, and breastfeeding. Breastfeeding is responsible for a high proportion of MTCT in developing countries, where studies show 30% or more of perinatal HIV infections occur through breast milk. Dunn et al. meta-analysis reported risk of transmission through breastfeeding to be between 7 and 22%, equivalent to a doubling of transmission rates. Van de Pere et al. findings showed the risk of breast milk transmission may also depend upon other factors, such as maternal disease stage, breast abscesses, mastitis, nipple cracks, maternal vitamin A, and oral thrush in the child. Our study showed two of the HIV-seropositive women had mastitis and four had nipple cracks. In addition, a Zimbabwe study showed 31% of breastfeeding mothers of HIV-1–infected children had active nipple disease. Breast milk has also been shown to contain both cell associated and free virus, the amount of which has been related to the immune suppression of the mother and vitamin A levels. Furthermore, the viral load in cervico-vaginal secretions and breast milk have been shown to be an important transmission risk intra partum and through breastfeeding. HIV-1 levels in these fluids have been shown in most studies to be correlated with CD4 count and viral load.
Transmission is also increased in the presence of high levels of maternal viremia. Our study revealed the mean CD4+ T-cell count was 429 cells/mm3 and the mean of the plasma viral load was 7830.5 RNA copies/mL. Studies have shown increased transmission in situations, such as in advanced disease, at the time of seroconversion, during the presence of high levels of p24 antigen anemia. Maternal levels of HIV are major risk factors in all forms of transmission whereas it has been shown that a rare polymorphism in the chemokine receptor CCR5 is the most protective. Transplacental HIV transmission has been shown as the least efficient form of MTCT despite the fetus exposure to maternal cells in utero. Nonetheless, a significant number of infants are exposed to HIV in utero, only 5–10% become infected. Our study also revealed that among the 114 HIV-seropositive mothers, 12 (12/114 = 10.52%) lost their babies a value similar to a previous finding reported in one of the healthcare centers. The mean CD4+ T-cell count among these women was 477.6 cells/mm3 and mean plasma viral load of 8918.5 RNA copies/mL. Ako-Nai et al. findings revealed HIV-seropositive pregnant women with ≤50,000 RNA copies/mL were often potential transmitters. Similar studies by investigators in Europe and New York have confirmed that more than half of women with viral load greater than 50,000 RNA copies/mL at the time of delivery have shown to transmit the virus.
The presence of STDs has also been known to affect viral shedding. The effect of coinfection of HIV, hepatitis, and T. vaginalis have also been shown to exacerbate transmission. Our study analyzed the effect of HIV–HBV coinfection among seven selected HIV-seropositive mothers in relation to means of specific parameters namely: CD4+ T-cell count and plasma viral load (RNA copies/mL). Our results showed the mean CD4+ T-cell count among the seven individuals at antenatal period was 327 cells/mm3 compared to 378.25 cells/mm3 at postnatal period. The plasma viral load was almost twice at antenatal period 8787 RNA copies/mL compared to 4705 RNA copies/mL, a reduction of almost two-fold.,, Analyses of the profile of the four others in whom T. vaginalis was involved (HIV–HBV–TV coinfection), the mean CD4+ T-cell count was 314.75 cells/mm3 compared to three individuals with only HIV–HBV coinfection whose CD4+ T-cell count was 405.3 cells/mm3. The viral load of the T. vaginalis “fueled” coinfection was 4375.5 RNA copies/mL compared to 1255 RNA copies/mL, a threefold decreased suggesting that T. vaginalis fueled HIV infection.
A California study involving African-Americans revealed Trichomonas vaginalis as one of the most effective cofactors in amplifying HIV transmission and also revealed that the pathology of individuals coinfected with T. vaginalis also increased HIV shedding. Also, the study noted that T. vaginalis infection increased/expanded the portal of entry for HIV in HIV-seronegative individuals. Furthermore, other investigators have reported that T. vaginalis aided transmission and in the acquisition of HIV, the prevalence of T. vaginalis was greater than the combined estimates of C. trachomatis and N. gonorrhoeae.
Our study analyzed breast milk samples and sera of HIV lactating mothers for levels of immunoglobulins [Table 5] and [Table 6]. Breast milk is shown to contain a rich array of factors that could potentially facilitate or hinder HIV transmission either directly or indirectly. Transplacental transmission, for example, tends to be inefficient as some protective antibodies in mothers serum and breast milk cannot cross the placental except IgG, which may assist in inhibiting microbial infections.
Studies have shown that in the absence of antiretroviral therapy, only 65% of HIV-infected children survive until their first birthday and less than half will reach 2 years of age. Combination antiretroviral therapy may be more effective in preventing transmission due to the greater reduction in viral load. Antiretroviral drugs reduce transmission of HIV-1, presumably by decreasing its levels in both maternal blood and maternal mucosal secretions, resulting in reduced infant exposure to the virus. Our study showed nine of these mothers had highest viral load and one of which was naaive on ARV. [Table 7], category C, revealed nine mothers with highest viral load that are potential transmitters., Overall, our data revealed that among the 114 HIV-seropositive mothers, 7.8% were potential transmitters.
| Conclusion|| |
Our data revealed the bacterial population of the vagina was highest (53.8%) followed by oropharynx 21.7%, nares of neonates 17.36%, and breast milk samples 7.1%, probably due mainly to microbiota of the vagina and pregnancy and are risk factors of MTCT. Predominant pathogens encountered were similar in the four sources (S. aureus, P. aeruginosa, C. diphtheriae), which posed a risk of immune suppression. The mortality rate for HIV-seropositive babies was 12/114 = 10.5%. The high rate of spontaneous vaginal deliveries (91.7%) posed high risk of MTCT. The fear, suspicion, and myth associated with elective caesarean section (C/S) is palpable among pregnant women in this region irrespective of their HIV serostatus, despite relentless counseling administered by clinicians and social workers. Education to reduce women's attitude to refusal to adopt elective caesarean sections despite assurance of its safety should continue in order to prevent MTCT (PMTCT). Unavailability and frequent changing of ARVs among HIV mothers during pregnancy pose a high risk of MTCT. The federal government of Nigeria is a beneficiary of a laudable program President's Emergency Plan for AIDS Relief (PEPFAR) jointly sponsored by the United States of America to eliminate HIV/AIDS in the country by providing free ART to all living with HIV/AIDS. It is, however, unfortunate that the Nigeria government has not been able to honor its own financial commitment to this program. So far, after 18 months of monitoring for MTCT in our study, only 2/70 = 2.85% infants were found reactive, indicating that the mortality rates seen may have been influenced by other risk factors such as rupture of membrane that occurred in one patient, prolonged labor in seven, coinfection with STDs in 62, and inconsistency with ART regime in 19 among the HIV-seropositive patients.
| Limitations|| |
Exclusive breast feeding could not be guaranteed in the course of the study among the participants. Constant change of ART created by out of stock of drugs was habitual in some clinics, which could have created sensitivity or resistance in HIV-1 strain, low participation of HIV-seronegative mothers in donating breast milk samples for analysis, also may have limited the amount of milk samples screened to significant numbers. The eighteen months life span of the study may have affected some of the parameters of MTCT.
The authors acknowledge Dr. V. Koledoye, Dr. P.O. Osho, Dr. Akintan Adesina, nursing staff of the HIV clinics and laboratory technologists at the four healthcare centres.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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Prof. Kwashie Ajibade Ako-Nai
Department of Microbiology, Faculty of Science, Obafemi Awolowo University, Ile Ife, Osun State
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]