Case Study MICR 420 Emerging and Re-Emerging Infectious Diseases, Spring 2010

1. Case StudyMICR 420 Emerging and Re-Emerging Infectious Diseases, Spring 2010 Case # 61 Daniel Ma Chakyra San Yessenia Velazco

2. Case Summary A 21-year-old male complains of nausea, vomiting, diffuse body aches, productive cough, fever, and loose, watery diarrhea. He had not urinated in the prior 24 hours and complained of dizziness on standing. His past medical history was significant for sore throat 3 weeks previously and a urinary tract infection “a month or two” ago. He no recent travel history, drank alcohol, and denied sexual contact. Physical Exam • Fever of 39.1°C, a heart rate of 104/min, and blood pressure of 134/84 mm Hg • Enlarged tonsils Lab • Fecal specimen positive for Entamoeba histolytica • Significant for white blood cell count of 2,200 (57% polymorphonuclear leukocytes, 33% lymphocytes, and 6% atypical lymphocytes) • Aspartate aminotransferase (AST) was 650 U/liter, • Normal range is 10 to 34 IU/L. • Alanine aminotransferase (ALT) was 830 U/liter • Normal range varies accordlingly • Lactate dehydrogenase (LDH) was 1,000 U/liter • Typical range is 105 - 333 IU/L • Hepatitis A, B, and C virus and HIV test were negative

3. Key Information Pointing to Diagnosis • Amebiasis (Entamoeba histolytica) • Symptoms include pain or discomfort over the liver, which is occasionally referred to the right shoulder, as well as intermittent fever, sweats, chills, nausea, vomiting, weakness, and weight loss. • Stool sample • Elevated AST (650 U/liter), ALT (830 U/liter), • Acute Human Immunodeficiency Virus (HIV) • Symptoms of fever and fatigue (and, often, rash). Other common symptoms can include headache, swollen lymph nodes, and sore throat (mono-like symptoms) • diminished WBC count (2,200) • Atypical lymphocytes (less than 10%) • Elevated AST (650 U/liter), ALT (830 U/liter), and LDH (1,000 U/liter)

4. The Diagnosis for Case # 61 • Primary infection • Acute HIV • Secondary infection • Amebiasis (Entamoeba histolytica) Even though HIV may be found in young, sexually active adults, we can't rule anyone out because of their age or that they don't fit a certain stereotype of HIV infected individuals.

5. Microbiology of HIV • Human Immunodeficiency Virus (HIV) • Retrovirus • RNA viruses (RNA is their basic genetic material) • Belongs to the lentivirus subgroup • HIV-1 produces the acquired immunodeficiency syndrome (AIDS) • HIV-2 produces a similar disease that is at present, largely restricted to West Africa. • Has the enzyme reverse transcriptase that can make DNA from the RNA and allow them to integrate into the host cell genome • HIV virus targets the host immune system • Infects CD4+ T cells and macrophages. • Characterized by a decline in T cell count and function, leading to a weakened immune system. HIV also induces B-cell polyconal activation and a lack of antibody specificity • Damages T helper lymphocytes (T4) because they have an antigen (CD4) on the surface of the cell. The CD4 receptors, plus a co-receptor, are the site of attachment for HIV. The viral envelope fuses with the cell membrane and releases the viral enzymes and two strands of RNA of the HIV genome • Viral GP-120 bind CD4 molecule on dendritic cells.  The fusion peptide will then bind to co-receptors CCR5 or CXCR4 and enter the cell

6. Pathogenesis of HIV • Acute infection is due to macrophagic -R5 HIV that infects macrophages, dendritic cells and T cells. R5 is 5-10 times more infectious than X4 virus. Later switch to X4 variants via reverse transcriptase mistake. X4 infects activated T cells in lymph nodes • “AIDS is primarily a consequence of continuous, high-level replication of HIV-1, leading to virus and immune-mediated killing of CD4 lymphocytes" • Gp120 binds CD4 which become targets of destruction and apoptosis • Downregulate MHC class 1 leading to NK cells killing • Syncytium formation • Primary acute infection: HIV Enter the host often through genital mucosa or intestinal mucosa. • CD4 T cell infection and depletion in the GI. Changes in gut mucosal allow translocation of HIV • Within 2 days: Dendritic cells infected with HIV migrates to the lymph and infects naïve CD4 T cells • Within 3 days: Systemic spread in blood stream and rapid division results in acute illness and “mono” like illness • HIV viral load increases while CD4 cell counts drop. • Seroconvert after 4-10 weeks • Latent period- with virus hiding in inactive T cells, memory cells in lymphoid tissues • Reservoir is the lymphatic system. • CD4 recover slightly, low viral load in blood • Early HIV stage- opportunistic infection, malaise occurs • CD4 decline correlates with viral load (-50/mm3 per year) • B cells get activated but may lead to polyclonal hypergammaglobulinemia, perturbation of cytokine expression. • Late Stage HIV- less than 200/ mm3 CD4 cells, severe infection, lymph node degeneration

7. Seroprevalence of Entamoebahistolytica in the context ofHIV and AIDS: the case of Vhembe district, in SouthAfrica’s Limpopo provinceA. Samieet al. (2010) • Background • Entamoeba histolytica is the causative agent of amoebic dysentery and amoebic liver abscess. • Distributed worlwide but it is more common in developing countries such as South Africa. • The parasite invades and destroys human tissue, causing haemorrhagic colitis and extra-intestinal abscesses. • A cell-surface adherence lectin mediates the parasite’s adherence to human colonic mucus, colonic epithelial • cells, and other target cells. • It is not clear yet, if the parasite has a significant impact on HIV or viceversa. • In this study, samples from HIV positive and HIV negative individuals were collected and tested for antibodies • reacting with the adherence lectin of Entamoeba histolytica. Results • Materials and Methods • Ethical considerations • Patients and sample collection • HIV testing and confirmation of HIV infections • Elisa for detection of anti-E. histolytica antibodies FIG. 1. The age-specific seroprevalences of Entamoeba histolytica in the subjects who were HIV-positive (■) or HIV-negative (□).

8. Earlier studies: - No clear association between E. histolytica infection and HIV in Mexico and Latin America (Moran et al., 2005) - No evidence of significant association between the presence of E. histolytica DNA in the stools of a subject and HIV status (Samie et al., 2006) - HIV-infected individuals with <200 CD4+ cells/µl were more likely to be seropositive for the amoeba than the HIV-positive subjects with higher CD4+ counts (Chen et al., 2007) • Discussion • HIV-positive individuals are known to be frequently co-infected with other organisms, the types • and prevalences of co-infections in South Africa largely remain to be elucidated. • In the present study, there was a significant difference between the seroprevalence of E. • histolytica infection recorded among the HIV-infected individuals and that recorded among the • HIV-negative. • The results from this study should be treated with some caution because of the limitations of • the study. • Limitations: • It was impossible to asses the level of association between seropositivity for anti-E. histolytica antibodies and the presence of diarrhea or liver abscess. • The immunodefiency caused by HIV infection is likely to give rise to more detectable co-morbidities in HIV-positive subjects than seen in HIV-negative subjects. • The completeness of the medical records of the present subjects could not be ascertained.

9. Diagnostic Tests for HIV • HIV is rarely diagnosed properly at clinics • Flu like or Mono like illness • Most patients seroconvert after 4-10 weeks of infection • This is why patient Ab was negative in our case • Due to the vague symptoms, complete sexual and HIV risk factor should be assessed. • ELISA-highly sensitive test used for first screening for Ab against virus HIV-1, types M, N, O and HIV-2 • Western blot confirms positive ELISA, often test for several proteins and the results reported as positive (2 or more protein), negative, or indeterminate. • Test for antigen such as P21 • Viral load test as an estimate viral replication marker using RT-PCR • Viral culture- expensive and time consuming and less sensitive. • Flow Cytometry- CD4 T cell count indicates risk of acquiring opportunity infections • Under 200 per microliter is AIDS • Lymph node biopsy • Genotyping of viral DNA to test for resistance

10. Therapy and Prognosis for HIV •  6 Classes of major antiviral drugs: • Non-nucleoside reverse transcriptase inhibitors • Nucleoside reverse transcriptase inhibitors • Protease inhibitors • Fusion inhibitors • Integrase inhibitors • Cellular chemokine receptor (CCR5) antagonists • HAART- highly active anti-retroviral therapy uses combination drugs • side effects includes liver damage, high blood sugar, high blood lipid, high lactate, bone loss, nerve problems, insomnia, vomit, fatigue. • Future treatment includes Antisense RNA, siRNA, anti-microbial peptide, vaccine • Treatment of secondary infection includes aggressive antibacterial and antifungal agents • Antiretroviral therapy is recommended in patients with CD4 counts between 350 and 500 cells/µL • Prognosis- The prognosis of untreated HIV infection is poor. The average time from infection to death is about a decade, although individual varies. • One report calculated that three-drug antiretroviral regimens increased life expectancy by 1.38 to 2.67 years at a cost of $13,000 to $23,000 per year • The rate of progression of HIV infections shows enormous individual patient variation

11. Prevention of HIV • Abstinence from sexual intercourse or stay in a long term monogamous relationship or use condoms • Abstain from sharing needles • Get tested for HIV and other STDs regularly, especially pregnant woman • Education and awareness • Health care professionals or people who may come into contact with infectious agents should be cautious. • Obtain medical treatment immediately after possible exposure • post-exposure prophylaxis. • Vertical transmission prevention: • Maternal testing, C- section, and avoid breastfeeding

12. Epidemiology and Threats • Population at risk is homosexual men • Males accounted for 74% of the population living with HIV • In the U.S., minority population have higher risk of infection. • 47%  black, 34% white, and 17% Hispanic. Asians/Pacific Islanders and American Indians/Alaska Natives~1%. • Globally, especially in developing countries, the rate of new infections is high, especially in young women • 26 million deaths have occurred in the past 30 years. • The development of drug resistant strains is a major threat • All HIV patients should be screened for drug resistant strains • Risk of superinfections with HIV and other pathogens • Only 10% of the HIV+ patients know their status • Vaccines are hard to make due to rapid evolution of HIV

13. What would you tell the patients? • The final diagnosis is HIV as primary infection. However, he has a secondary infection caused by a parasite known as Entamoeba histolytica. • There is a difference between having HIV and AIDS. The development of AIDS can be delayed by using retrovirals and avoiding secondary infections. • He needs to avoid sick people and protect himself from acquiring any infection that will depress his immune system. • HIV patients need emotional support from their families and friends.

14. Take Home Message • Acute HIV occurs after transfer of body fluids from an infected person to an uninfected one • period is characterized by rapid viral replication that leads to an abundance of virus • Typical symptoms includes: • Fever, swollen lymph nodes, sore throat, and fatigue • Pathogenesis is the rapid viral replication that leads to decline of CD4 T cells that results in AIDS and numerous infections • Diagnostics include ELISA to screen for antibody followed by Western Immunoblot. Other tests includes PCR, antigen test, and viral culture. • Therapy is based on HAART using a combination of several antiviral drug classes • Prognosis is generally poor without treatment. With treatment individual disease progression varies. • Prevention is via education, safe sexual practices, and avoid sharing needles • Transmission is via body fluids, blood, sexual activity, sharing of needles, and vertical transmission from mother to fetus. • Threat is the potential of drug resistance strains and world wide epidemic

15. Questions? “Time to get some points!”

16. References • www.uptodate.com Accessed May 28th, 8:12PM • www.cdc.gov, accessed June 1st, 10:45PM • www.emedicine.medscape.com accessed May 26th, • Samie, A., et al (2010) Seroprevalence of Entamoeba histolytica in the context of HIV and AIDS: the case of Vhembe district, in South Africa’s Limpopo province Annals of Tropical Medicine & Parasitology, Vol. 104, No. 1, 55–63 (2010)

17. Point Spread