Dr Anil Sabharwal Md

HIV Dr Anil Sabharwal MD

• AIDS was first recognized in the United States in the summer of 1981, • Unexplained occurrence of Pneumocystis carinii pneumonia in five previously healthy homosexual men in Los Angeles • Kaposi's sarcoma (KS) in 26 previously healthy homosexual men in New York and Los Angeles. • Within months, the disease became recognized in male and female injection drug users (IDUs) and soon thereafter in recipients of blood transfusions and in hemophiliacs. • It became clear that a microbe transmissible by sexual (homosexual and heterosexual) contact and blood or blood products was the most likely etiologic agent of the epidemic

• In 1983, HIV was isolated from a patient with lymphadenopathy • 1984 it was demonstrated clearly to be the causative agent of AIDS. • In 1985, a sensitive enzyme-linked immunosorbent assay (ELISA) was developed,

AIDS • 1st recognized in US 1981 • In 1983, HIV was isolated from a patient with lymphadenopathy, • In 1984 it was demonstrated clearly to be the causative agent of AIDS. • In 1985, a sensitive enzyme-linked immunosorbent assay (ELISA) was developed

HIV I & II • HIV, which belongs to the family of human retroviruses –RNA virus-HIV-1 (subtypes A,B,C,D,AE )and HIV-2, HIV2 –differs from HIV 1• patient has lower viral load • Slower CD-4 decline, • Lower rate of viral transmission • Slower progress to AIDS

TRANSMISSION: • Major route heterosexual(>75%) • HIV is transmitted by homosexual & heterosexual contact • Blood and blood products-lab workers; • Infected mothers to infants either intra partum, perinatally, or via breast milk. • There is no evidence that HIV is transmitted by casual contact or that the virus can be spread by insects, such as by a mosquito bite. • World wide there are 40 million persons infected with HIV

CD4 & CD8 cells • After entry HIV is transported to LN via CD4 cells • CD4 cells (helper inducer) are responsible for cell mediated immunity • Any ↓ in CD4 count→ opportunistic infection & onchogenic virus related tumors • ↓CD4 cells is correlated with virus load • CD8 cytotoxic T cells bind & Lyse infected CD4 cells

• B lymphocyte ¯ophages are also infected→↓ humoral immunity • CD4 count provides important prognostic information

Clinical features of primary infection • Many patients with HIV infection remain asymptomatic with a mean time of 10 years between exposure development of AIDS • However hairy lucoplakia & oral thrush should raise suspicion of HIV • Fever with rash • Pharyngitis with cervical lymphadenopathy • Myalgia/arthalgia • Headache • Mucosal ulceration

• Fever, night sweats, weight lost Pneumocystitis pneumonia is most common opportunistic infection associated with AIDS & is difficult to diagnose because symptoms –fever, cough & dyspnea are nonspecific • Diagnosis-chest X-ray-diffuse or perihilar infiltrates

CNS • • • • •

Toxoplasmosis-most common AIDS dementia complex Cryptococcus meningitis HIV myelopathy progressive multifocal leucoencephalopathy

Others • • • • • •

Myopathy Retinitis Oral lesion-candidiasis or hairy leucoplakia GIT-candidal esohagitis,hepatic dis Endocrinal-hypogonadism Skin-Herpes simplex,, herpes zoster, mmolluscum contagiosum

HIV related malignancies • • • •

Kaposi sarcoma Non-Hodgkin’s lymphoma Primary lymphoma of brain Non-invasive cervical carcinoma

Lab investigations • HIV-ELISA-screening test,15% +ve in 3 weeks, 95% in 6wks • Western blot-confirmatory test, • HIV rapid antibody test-screening test • CBC-anemia, neutropenia, thrombocytopenia • Absolute CD4 count risk of opportunistic infection or malignancy ↑ when CD4<200cells/mcl • CD4 lymphocyte percentage-risk↑ if %<20 % • HIV viral load tests-measure amouunt of actively replicating virus

Prevention-Primary • • • • • • •

No vaccine Education Effective precautions regarding sexual practices Injection use Screening of blood products Perinatal HIV prophylaxis practice Precautions for lab technicians & blood handlers

Secondary prevention • AIDS develops in 10 years in 50 % of sero positive persons in untreated patients • ↓in incidence of A IDS reflecting successful treatment of HIV & successful HIV prevention is reported in USA & Europe • Prophylactic regimen can prevent opportunistic infection & improve survival

HIV risk for health care professional • Needle stick injury :risk of HIV transmission is 1:300.Testing done at 6 weeks 3 months & 6 months • Zidovudine following a needle stick injury ↓ HIV seroconversion by 79 %

Preventing perinatal transmission • Zidovudine given to mother during pregnancy, labour & delivery & to their newborns rate of HIV transmission ↓by 2/3rd • Breast feeding ↑the rate of transmission by 10-20 %

Treatment 1. Therapy for opportunistic infection& malignancy 2. Antiretroviral treatment 3. Hematopoietic stimulating factor (erythropietin) 4. Prophylaxis of opportunistic infection

Antiretroviral Drugs • • • • •

Zidavudine Lamivudine Abacavir Tenofovir Enfuvitide

Cerebral Malaria

Malaria • 4 species of Plasmodium – P. vivax, P. Malariae, P. Ovale & P.falciparum • Malaria transmitted from person to person by bite of infected female anopheles mosquitoes • Resistance of vector to insecticide continue to ↑ • Congenital transmission &through blood transfusion • No animal reservoir for human malaria

Cycle in mosquito • Mosquito gets infected by ingesting human blood containing sexual forms of parasites(micro & macrogametocytes).In salivary glands the gametocytes develop into sporozoites.In next bite sporozoites are injected into human blood

Cycle in Human • Sporozoites reach liver through RBC where merozoites are formed. merozoites again infect RBC to repeat the cycle of fever • In vivax & ovale some sporozoites become inactive (hypnozoite) Reactivation of hypnozoite can occur after 6-8 months→ relapse • In falciparum & malarae hepatic phase is not there so radical treatment is not required.

Clinical features • Cold stage-shaking chills-4-6 hours • Hot stage-fever 410c or higher • Sweating stage Fever is either daily or alternate day Other features-headache, dizziness, GIT symptoms-nausea ,vomiting ,pain abdomen Splenomegaly after 4 or more days of fever

Falciparum Malaria • P Falciparum is serious infection & may prove fatal because of heavy parasitemia (20%)→sequestration of RBC in capillaries • Complications: 1)hypotension & shock, 2) cerebral malaria,3)hemolytic anemia.4) acute tubular necrosis (black water fever) 5)cardic arrhythmia ,6)DIC 7) pulmonary oedema,

Lab investigation • Thick & thin PS-Giemsa stained – samples to be taken at the time of shivering • Antibody test + ve after 8-10 days,but can not differentiate current from past infection • ↓ hb

Prevention • Prevention of mosquito bite • Empirical treatment • Treatment-

Typhoid Fever • Salmonellae are transmitted to humans orally by contaminated food or water. The bacteria traverse the gastrointestinal tract, including the acidic environment of the stomach, to colonize the small intestines. In the case of enteric fever (a systemic illness), salmonellae cross the intestinal barrier, where phagocytosis by macrophages results in their dissemination throughout the reticuloendothelial system

• In enteric (typhoid) fever, salmonellae (S. typhi or S. paratyphi) undergo phagocytosis by macrophages after crossing the epithelial layer of the small intestine. Once phagocytosed, the bacteria are protected from polymorphonuclear leukocytes (PMNs), the complement system, and the acquired immune response (antibodies). Salmonellae have evolved mechanisms to avoid or delay killing by macrophages.

Clinical Features • • • • •

Prolonged fever (38.8° to 40.5°C, or 101.8° to 104.9°F). Gastrointestinal symptoms - diarrhea or constipation Abdominal rash ("rose spots"), hepatosplenomegaly, epistaxis, and relative bradycardia.

Complications Late complications,in the third and fourth weeks of infection, are most common in untreated adults and include intestinal perforation and/or gastrointestinal hemorrhage. Both complications are life-threatening and require immediate medical and surgical interventions, with broadened antibiotic coverage for polymicrobial peritonitis

Rare complications • pancreatitis, hepatic and splenic abscesses, endocarditis, pericarditis, orchitis, hepatitis, meningitis, nephritis, myocarditis, pneumonia, arthritis, osteomyelitis, and parotitis. • Despite prompt antibiotic treatment, relapse rates remain at ~10% in immunocompetent host

Carrier • Approximately 1 to 5% of patients with enteric fever become long-term, asymptomatic, chronic carriers who shed S. typhi in either urine or stool for >1 year. The incidence of chronic carriage is higher among women and among persons with biliary abnormalities (e.g., gallstones, carcinoma of the gallbladder) and gastrointestinal malignancies.

Diagnosis • The diagnostic "gold standard" is a culture positive for S. typhi or S. paratyphi • Blood cultures is +ve in 90% during the first week of infection and 50% by the third week • A diagnosis can also be based on positive cultures of stool, urine, rose spots, bone marrow, and gastric or intestinal secretions. • Bone marrow cultures remain highly (90%) sensitive despite 5 days of antibiotic therapy. • Widal test for "febrile agglutinins," are available; however, given high rates of false-positivity and false-negativity, these tests are not clinically useful

Treatment • Ceftriaxone (1 to 2 g intravenously or intramuscularly) for 10 to 14 days is equivalent to oral or intravenous chloramphenicol in the treatment of susceptible strains. • Quinolones -Ciprofloxacin (500 mg orally twice a day for 10 days).Ofloxacin (10 to 15 mg/kg in divided doses twice daily for 2 to 3 days) .

Prevention • Improvements in food handling and water/sewage treatment, enteric fever has become a rare occurrence in developed nations • Vaccine-oral & injectable.