1. Vitamin A Deficiency in Pregnant Women with and without HIV Infection in Ethiopia Afework Kassu, Andargachew Mulu College of Medicine and Health Sciences, University of Gondar, Ethiopia. afeworkkassu@yahoo.com 16 th ICASA, Addis Ababa, Ethiopia Dec 4-8, 2011

2. Bidirectional interaction between nutrition, immune function and infection Diminished host defense Undernutrition Infection Pathogen Undernutrition impairs immune defenses and lowers resistance to invading pathogens. In turn infection alters nutrient status and contributes to the undernourished state

3. Activation of inflammatory/immune responses INFECTION AnorexiaMalabsorptionIntestinal damageDiarrhea Decreased nutrient intakeDecreased nutrient absorptionNutrient loss Increased metabolic rateRedistribution of nutrients Increased nutrient requirement Mechanism by which infection can affect nutrient status

4. Vitamin A is an essential micronutrient required for vision, growth, reproduction, cell proliferation, cell differentiation, and the integrity of the immune system. Anti-infective vitamin due to the consistent synergy between its nutritional deficiency and the incidence of infectious diseases Supplementation reduces infectious disease morbidity and mortality among women and children in developing countries Vitamin A

5. Vitamin A deficiency (VAD) Significant public health problem among women of reproductive age in Africa and South-East Asia VAD in women has negative consequences on their health status as well as on their infants VAD in pregnant women is associated with: -night blindness, -severe anaemia, -wasting, malnutrition, -reproductive and infectious morbidity, -increased risk of mortality

6. VAD: - reduces lymphocyte response, - leads to reduced levels of secretory IgA in mucous membranes - weakens the local barriers to infection Vitamin A deficient women were found to be more susceptible to both infectious (such as frequent infection of mucous surface of hallow viscera) and non-infectious (eclampsia, preeclampsia, premature rupture of membrane) diseases

7. Observational studies in sub-Saharan Africa have shown that, low serum vitamin A levels in HIV-infected women to be associated with significantly increased rates of MTCT of HIV and infant mortality In Ethiopia, a country where micronutrient deficiencies and HIV infection are highly prevalent, studies on vitamin A status and magnitude of VAD in pregnant women in the context of HIV infection are scarce

8. A better understanding of the interrelations between HIV infection and vitamin A status is necessary to conduct accurate assessment of the need for and potential benefits of interventions (vitamin A supplementation). Rationale Objectives To investigate the serum levels of vitamin A in pregnant women with and without HIV co-infection.

9. Gondar University of Gondar Hospital, Gondar, Northwest Ethiopia. Tertiary level hospital, 400 beds, rendering outpatient, inpatient and referral health service to over 5 million people in Northwest Ethiopia. Study site

10. Pregnant women who visited the antenatal clinic of the University of Gondar Hospital ANC clinic in their first trimester for routine antenatal care. Apparently healthy non-pregnant women, who were living in the same geographic locale as pregnant participants, were recruited from voluntary blood donors and served as controls None of the subjects had cirrhosis and none of them received vitamin A supplementation. Informed consent was obtained from the study participants Study protocols approved by Institutional Research Ethics Committee Participants

11.  Socio-demographic data: Questionnaire  Diagnosis of HIV infection - Enzyme immunoassay: following national algorithm  Determination of serum vitamin A - High performance liquid chromatography - VAD: serum retinol level below 0.70  mol/L  Statistics: - SPSS software, ANOVA, students t test, Chi Square test Methods

12.  Pregnant Women (n=423) Results HIV-: 379 (89.6%) Age: 25.5 ± 4.9 HIV+: 44 (10.4%) Age: 25.4 ± 5.8 HIV-: 25 Age: 26.3 ± 5.9 HIV+: 30 Age: 29.6 ± 6.7  Non-pregnant Women (n=55)

13. Mean level of vitamin A in pregnant women co- infected with HIV vs pregnant women without HIV infection Serum retinol (μmol/L) P=0.02 P<0.001

14. % VAD N=44 N=379 VADVAD – severe public health problem in pregnant women P<0.001 Proportion of pregnant women with HIV infection who were deficient for VA was significantly higher compared to that in pregnant women without HIV infection

15. Mean serum vitamin A concentration (µmol/L) in HIV seropositive pregnant women (0.96±0.42, n=44) was significantly lower than that in HIV seronegative pregnant women (1.10±0.45, n=379, P=0.02). VAD was observed in 25% and 17.7%, respectively, of pregnant women with and without HIV co- infection. These indicate that VAD is a public health problem in pregnant women in Gondar, Ethiopia. Limitations of the study: acute phase response, clinical signs of VAD, and dietary intake not determined. Summary

16. VAD from other studies in Africa 50-63% South African pregnant women [Moodley et al S Afr Med J 1998, 88:1029-32] 63% Zambian patients with persistent diarrhea [Kelly et al AIDS 1999, 13:495-500] 29% Rwandan tuberculosis patients co-infected with HIV [Rwangabwoba et al IJTLD 1998, 2:771- 73] 90% of Tanzanian tuberculosis patients [Mugusi et al IJTLD 2003, 7:804-807] 63% Ethiopian tuberculosis patients [Kassu et al Nutr Res 2007]

17. Low serum levels or low intakes of vitamin A in HIV-1 infection have been associated with: Lower CD4+ cell counts [Semba et al Arch Intern Med 1993, 153:2149-2154] Immune abnormalities - impaired antibody mediated immunity and barrier defense [Semba Nutr Rev 1998, 56:S38-S48] Increased maternal-fetal HIV transmission [Semba et al Lancet 1994, 343:1593-1597] Increased risk of progression to AIDS [Tang et al Am J Epidemiol 1993, 138:937-951] Increased mortality from AIDS or infections [Semba et al JID 1995; 171:1196-1202] Increased risk of preterm delivery and maternal anemia [Radhikaa et al, BJOG, 2002, 109:689- 693]

18. Infection vs VAD Infections contribute to deficiencies of vitamin A due to: -Reduction in dietary intake: Due to anorexia, depression, oral sores -Malabsorption: infection of gastrointestinal cells -Increased loss: Diarrhea-related/urinary losses -Altered metabolism: Impaired transport, storage, utilization These complex interactions between malnutrition and infection would lead into mutually reinforced detrimental clinical effects: - immune deficiency - rapid disease progression - mortality

20. Intervention programs involving health and nutrition education might help in improving vitamin A status of pregnant women Further in-depth studies to substantiate the present findings and also to assess whether supplementation of vitamin A is required to benefit pregnant women Recommendations

21. University of Gondar, Ethiopia Prof Yared Wondimkun Mr Belay Tessema The University of Tokushima, Japan Sasakawa Scientific Foundation, Japan. Prof Fusao Ota Prof Shigeru Yamamoto Dr Masayo Nakamori Dr Nhien van Nguyen Castle of Gondar Acknowledgements

22. Multi-ethnic country Ethiopia: multiethnic Thank you all.