INTRODUCTION:
Opportunistic infections (OI) are the hall mark of immunodeficiency associated with HIV. They include opportunistic protozoan, fungal , bacterial , viral and other infections along with repeated episode of HIV infection. It is important to diagnose OIs, because acute infections are at times life threatening, effective prophylaxis result in better survival. The clinical manifestations are different than normal host. Various studies established the relationship between rising viral load and decreasing CD4+ count and progression of HIV. Timely chemoprophylaxis reduce the risk of OIs and effective ART therapy (anti retroviral) decreases viral load, restore immune function, reduce risk of OIs.

Certain patients in the developed and developing world do not have access to care or response to ART due to multiple reasons leading OIS as important cause of morbidity and mortality in HIV-1 infections. The therapy for OIs has changed substantially leading to new strategies for management.

CLASSIFICATION
AIDS (CDC classification category C diseases) is defined by the development of specified opportunistic infections or tumours. There is a correlation between CD4 count and HIV related infections.
TABLE – 1(CD4 COUNT AND ASSOCIATED INFECTIONS)
> 500 cells/mm3 Acute primary infection, Recurrent vaginal candidiasis
<500 cells /mm3 Pulmonary Tuberculosis, Pneumococcal pneumonia, Herpes Zoster, Oropharyngeal candidiasis, Extraintestinal salmonellosis, Lymphoid interstitial pneumonitis
<200 cells/mm3 Penumocystis carinii (jirovecii)pneumonia, Mucocutaneous herpes simplex, Cryptosporidium, Microsporidium, Oesophageal candidiasis, Miliary/extrapulmonary tuberculosis
<100 cells/mm3 Cerebral toxoplasmosis, Cryptococcal meningitis
<50 cells/mm3 CMV retinitis, CMV gastrointestinal diseases, Disseminated mycobacterium avium intracellulare
The Ols can be descried as per the system involved.
1. Pulmonary diseases seen in HIV (OIs)
• Bacterial: Streptococcus penumoniae, H. influenzae, Pseudomonas aeruginosa, Klebsiella penumoniae, Rhodococcus equi, Mycobacterium tuberculisis, Atypical mycobacteria
• Fungal: Penumocystis carinii (Jirovecii), Cryptococcus neoformans, H. Capsulatum, Coccidiodes emitis, Penicillium marneffi, Aspergillosis
• Viral - CMV, EBV, HSV, VZV
• Protozoal – Toxoplasma gondii, Strongyloides stercoralis
2. CNS
• C. Neoformans
• Toxoplasma Gondii
• JC Virus causing PML
• Others : Syphillis, M. tuberculosis, T. cruzi, HTLV – I infection, Acanthamoeba
3. G.I.T
• Fungus – Candidiasis, Histoplasma, Coccidioidomycosis, Penicillisis
• Bacterial – Salmonellosis, Shigella, Campyolobacter jejuni
• Virus EBV – (Oral Hairy leucoplakia)
CMV Colitis, Rotavirus, Adenovirus , HSV
• Protozoal infection : Cryptosporidiasis, Cyclospora, Micosporidiasis, E. histolytica, Isosporiasis, G. lamblia, C. difficile
4. Hepatobiliary – HBV and HCV infection
Fungus – C.immitis, Histoplasma
5. Genitourinary – Syphilis, candidiasis
6. Dermatological Condition
• Seborrheric dermatitis, Herpes simplex / Varicella zoster virus (VZV), Bacillary angiomatosis, Molluscum Contagiosum, Anogenital HPV (Human papilloma virus), Scabies, Syphilis, Fungal folliculitis rash (Fungal – Malassezia furfur), Dermatoplytic infections involving skin, nail
7. Cardiovascular
Cardiomyopathy – Cryptococcosus, Chagas disease, Toxoplasmosis
Pericardial Effusion - Tubercular
8. Rheumatological
Septic arthritis may be due to fungus C. neoformans, H. capsulatum, Sprorothrix schenckii, Systemic mycobacteria – M. haemophillum
9. Endocrine System
Adrenal gland involved in CMV, mycobacterial, cryptococcal, histoplasmosis
Thyroid – involved in P. carinii, CMV, toxoplasma, mycobacterial, cryptococcal
10. Haemopoetic System
Bone marrow suppressed by – Fungal, Mycobacterial and B19 parvovirus
11. Ophthalmic Disease
CMV Retinitis
HSV & VZV
P. Cariniii – Choroiditis
Toxoplasma - Chorioretinitis

Few common Ols are described in the paragraph following.


P.C.P. (Pneumocystis carnii pneumonia):
Very common infection and called as “ AIDS pneumonia”, occurring in 57% of children below 1 year and leading cause of interstitial plasma cell penumonia. It is a protozoan but closely related to fungi. The reservoir and mechanism of transmission is obscure but transmittd by direct air borne. The organism establishes in alveoli where it proliferates as an exracellular parasite producing interstitial oedema, hyaline membranes resulting in progressive hypoxemia and respiratory failure. The symptom tetrads are fever, cough, dyspnoea and tachypnea. Physical examination shows tachycardia, respiratory distress with accelerating tachypnoea and diffuse retraction without any specific auscultatory findings. Extrapulmonary penumocystitis involves L. node, spleen, liver, Thyroid, adrenal gland, kidney. Ophthalmic lesion of choroids, necrotising vasculitis resembling Burger’s disease, bone marrow hypoplasia, intestinal obstruction, heart. Associated with cystic lesion or calcification on CT or Ultrasound. Otic involvement cause polypoid in auditory canal.

Arterial blood gas analysis (ABG) shows progressive hypoxemia, respiratory failure. Chest X-ray shows signs of hyperinflation with peribronchial thickening , bilateral alveolar, interstitial in filtration, which spread outwards from hila. Further progression leads to bilateral airspace disease with air bronchogram, cavities, pleural effusion and spontaneous penumothorax, the last being characteristic.

The diagnosis is confirmed by Wright – Giemsa staining of induced sputum or Broncho-Alveolar Lavage (BAL). Trophozoites and intracystic trophozoites are seen. Prognosis is related to hypoxaemia (Alveolar – arterial O2 gradient - < 35 mm of Hg – Mild, 35-45 mm of Hg moderate and > 45 mm of Hg severe).

Treatment: The treatment is a medical emergency. The treatment of choice is Trimethoprim sulphamethoxazole (TMP-SMX) or Pentamidine. The other alterantive drugs used in adults are Dapsone – TMP, Clindamycin, Primaquine, Atovaquine.
TABLE – 2
Drug Schedule Remark
TMP-SMX 20mg of TMP/Kg/Day in 4 divided doses I/V for 21 days Restore to oral when patient responds
Pentamidine 4mg/Kg/Day,
Single Dose, I/V for 21 Days Reserved who cant tolerate TMP- SMX or no response after 7 days of therapy.
Dapsone – TMP
Clindamycin
Primaquine
Atovaquine
Mortality – 5-40% in treated and 100% in untreated cases.

PREVENTION:
Indication: All HIV infected children from 4 weeks to 12 months of life, in determinate status children from 4 weeks till HIV is excluded (4 months), HIV infected children above 1 year having CD4 count of < 500 (1- 5years) and < 200 (6-12 years). All children who have been treated for PCP.
TABLE – 3
Drug Schedule Side Effect
TMP-SMX • 150 mg of TMP/M2/day. Orally in two divided doses on 3 consecutive days of a week.
• 150 mg of TMP/M2/ day orally divided into 2 doses on 3 alternating days. Aplastic anaemia megaloblastic anaemia, Steven – Johnson’s Syndrome, Neutropenia, Thrombocytopenia
Dapsone 2mg/Kg/Day orally
(Max – 100mg) Methemoglobinemia
Haemolytic anaemia
Pentamidine (inhaled) 300mg of Pentamidine isoethionate inhaler every 28 days Cough, bronchospasm , increased risk of extra pulmonary PCP
Pentamidine (I/V) 4 mg/Kg /Day single dose I/V every 2-4 weeks Hypoglycemia, Hyperglycemia, Hypertension, Hypocalcaemia, rash

Rhodococcus Equi – Gram +ve pleomorphic acid – fast nonspore forming bacillus causing pulmonary or /and disseminated infection. Presents as fever cough. Chest X-ray show cavity or consolidation. Blood culture may be +ve treated with proper antibiotic.

TUBERCULOSIS:
In high prevalent areas primary and reactivation of tuberculosis is common due to depressed cell mediated immunity. Drug resistance is also common. The extensive tuberculosis is due to progressive depletion and dysfunction of CD4 cells with macrophage and monocyte dysfunction.

Clinically present as fever, cough, weight loss, night sweat, malaise. Extrapulmonary manifestation like CNS (meningitis), lymphadenopathy, hepatosplenomegaly, genitourinary, mastoid involvement occur. The disease may be extensive (miliary).

Diagnostic difficulty is due to unusual features (Tuberculin – ve) and extrapulmonary manifestation. History of contact, tuberculin test (induration > 5 mm), chest X-ray showing lobar or multilobar infiltration or diffuse interstitial lesion and hilar adenopathy are clue. Isolation of AFB from gastric lavage, BAL, sputum is gold standard test. The samples collected from pulmonary and extrapulmonary tissue subjected to culture and sensitivity to drugs as drug resistance is very high. PCR test on sputum , pleural fluid, CSF is highly sensitive and specific.

Treatment:
1st Line Drugs:
INH – 10-20 mg/kg/day (max 300mg)
Rifampicin – 10-20 mg/kg/day (max 600mg) – (May lower the concentration of antiretroviral drugs as it induces the action of hepatic cytochrome 450).
Pyrizinamide - 30 mg/kg/day
Ethambutol - 15 mg/kg/day
Streptomycin – 20-30 mg/kg/day IM
Rifabutin – 300mg for 4 months
2nd Line Drugs:
Ofloxacin, Ethionamide, Cycloserine, Capreomycin, PAS

Duration of Treatment:
• For pulmonary TB – 6-12 Months
• For extrapulmonary TB – Minimum 12 Months
• DOT (Directly Observed Therapy) may be given during initial phase.
• Children of Mx positive without any other lesion – INH & Rifampicin for 12 months.
• In MDR TB – 6-7 drugs depending on sensitivity for 12-15 months.
To start ART the CD4 count is a guideline (WHO recommendation).
• CD4 count < 200/L – Start ATT first and ART is started as soon as patient tolerate ATT (Takes 2-4 weeks).
• CD4 count 200 to 350/L – Start ATT and add ART after intensive phase –(8weeks).
• CD4 count > 350/L – Treat TB completely and defer ART.

NON-TUBERCULOSIS MYCOBACTERIAL INFECTIONS
Mycobaacterium avium complex (MAC) includes M. kansasii, M. Chelonei and M. fortuitum which are saprophytes present in soil, water, food and infect when CD4 count is below 50 cells/ml. Lung, liver, spleen and lymphnodes, bone marrow and GIT are the common sites. Incidence is less in India. Transmitted by inhalation or ingestion. Lung is an unusual site of infection.

Slow progressive clinically present as high fever, weight loss, anemia, abdominal pain, night sweat, diarrhoea, malaise, hepatomegaly, osteomyelitis, meningoencephalitis, intraabdominal and soft tissue abscesses.

Peripheral smear shows anaemia, neutropenia, chest X-ray shows nonspecific finding like focal, diffuse infiltration, cavity, hilar adenopathy. Culture of blood or tissue by Radiometric assay show +ve in two weeks. PCR can identify the species. Biopsy from liver, L. node or marrow shows AFB bacillus within macrophages.

For treatment Azithromycin (10 mg /kg/day – single dose), Clarithromycin (15 mg /kg/day – 2 divided dosees), Ethambutol (15-20 mg /kg/day – single dose), Rifabutin (5-10 mg /kg/day – single dose) Ciprofloxacin (20-30 mg /kg/day Orally– single dose) Amikacin are given. The regimen includes 2-4 drugs i.e Azithromycin or Clarithromycin with Ethambutol and/or Rifabutin and Ciprofloxacin or Amikacin. Immunomodulators like GM-CSF, G-CSF, Interferon gamma, interleukin –2 are helpful.

For primary prophylaxis any drug is given for periods depending on CD4 count (< 50 – 6years, <75 2 –6 years, < 500 – 1-2 years, < 750 – 12 months). Secondary prophylaxis in patients suffering from MAC is life long including at least two drugs.

TOXOPLASMA GONDII INFECTION
In children manifest as congenital toxoplasmosis and CNS manifestation. Pregnant Mother transmit to fetus.

Congenital toxoplasmosis present as low birth weight, microcephaly, hydrocephalus, hepatosplenomegaly and chorioretinitis. CNS toxoplasmosis present as fever, headache, seizures, psychosis, altered sensorium and focal meurological deficit as hemiparesis, ataxia, cranial nerve palsy, aphasia, cerebral edema, confusion, dementia, coma.
Demonstration of specific IgM and IgA antibodies in serum is diagnostic of congenital toxoplasmosis. CNS toxoplasmosis is diagnosed on clinical ground, presence of IgG antibodies and multiple ring enhancing granulomatous lesion on CT scan or MRI. Brain biopsy is definitive diagnosis.

TREATMENT
Sulphadiazine – Loading 100mg/kg followed by 85-120mg /kg/day in 2-4 divided doses. Pyrimethamine – 1-2 mg /kg/day for 2 days followed by 1 mg/kg/day for 2-6 months and 1 mg /kg/day up to 1 year. Folinic acid (calcium leukovorin) 5-10 mg /kg/day or alt days to prevent megaloblastic anaemia secondary to pyrimethamine. Prednisolone 1 mg/kg/daily orally in active chorioretinitis or CSF protein is > 1gm%. Clinadmycin (20 mg/kg/day in 4 divided doses), pyrimethamine, folinic acid is alternate regimen.
CNS Toxoplasmosis: - The drugs used are pyrimethamine and sulfadiazine or Trisulfapyrimidine. Folinic acid is given to prevent bone marrow suppression. Relapse is common which requires reinstitution of therapy.
An episode of CNS toxoplasmosis requires life long prophylaxis.

VIRAL INFECTIONS
The common viruses are Herpes Simplex Virus (HSV 1 & 2), Cytomegalo Virus (CMV), Varicella Zoster Virus (VZV), Epstein Barr Virus (EBV) and Human Herpes Virus type – 8 (HHV-8). The infections are often chronic, invasive and fatal with HIV infection.
1. HSV 1 & 2: HSV-1 is transmitted through contact with oral mucosa and salivary secretions. HSV2 transmitted sexually and present as anogenital lesion. When CD4 count is > 100/mm3 both present as recurrent self-limited cluster of orolabial ulcers, genital, anorectal ulcers. In lower CD4 count the vesicular lesions are found at other sites. In severe cases there are large, painful ulcer which slowly resolve. Stomatitis follow oral lesions and fissures and fistula follow rectal and genital ulcers. Bacterial infection may supervene. Advanced AIDS cases with low CD4 count may produce systemic HSV-infection producing oesophageal ulcer (odynophagia, chest pain)pneumonia, hepatitis, meningoencephalitis, ventriculitis, shock, sepsis like syndrome and transverse myelitis.
Diagnosis is based on typical clinical lesion, rising antibody titre, isolation of virus from culture, detecting HSV1 & 2 antigen from skin or mucosa by scraping and immunofluorescent stain. In suspected HSV encephalitis HSV DNA in CSF using PCR is useful.
Acyclovir is drug of choice. In neonates and severe HSV infection given in a dose of 30 mg/kg/day in 3 divided doses for 2-3 weeks. Primary gingivostomatitis or genital HSV are treated with oral Acyclovir 80mg/kg/day in 3 divided doses for 10 days. Famcyclovir or Valacyclovir in a dose of 750- 1500 mg/day in 3 divided dose may be used. Foscarnet in a dose of 120mg/kg/day on 2-3 divided doses in Acyclovir resistant cases.
For prophylaxis in HIV patients with frequent or severe relapse or slow healing lesion Acyclovir 200mg tid or 400mg bid orally is given.
2. Vericella Zoster Virus (VZV):
In immunocompromised patients causes greater morbidity and mortality. Clinically presents as fever with generalized pruritic rashes (typical). They may be chronic, recurrent, persistent (appearance of new lesion for > 1 month), sever in advanced cases. In chronic infection the skin lesion become verrucous or necrotic. In severe infection presents as high fever, numerous skin lesion, systemic involvement like pneumonia, encephalitis, hepatitis.
Demonstration of VZV antigen in skin lesion, isolation of virus from vesicle contents, rise in antibody during convalescence and VZV specific IgM antibody confirm the diagnosis. PCR is also extremely sensitive and specific.
In severe cases Acyclovir in a dose of 1500mg /M2/day in 3 divided doses for 7-10 days or till no new lesions appear whichever is later is given. In mild cases Acyclovir is given orally 80mg/kg/day in 4 divided doses.
HIV infected children exposed to chickenpox are given varicella zoster immunoglobulin (VZIM) within 96 hours in a dose of 1 vial/10kg (maximum 5 vials). For recurrent case daily Acyclovir is given.
3. Herpes Zoster:
It is a dormant form of VZV producing painful vesicular lesion affecting dermatomes in immunocompetent persons.
Clinically presents as multidermatomal infection, dessiminated Zoster, bilateral rash, retinitis, rarely penumonitis, consumptive coagulopathy, hepatitis, marked constitutional symptoms and encephalitis. Chronic and relapsing cases and post herpetic neuralgia are common.
Classical dermatomal distribution of painful, vesicular eruption is diagnostic. Confirmed by virus isolation and detection of viral antigen in the skin.
Severe cases or neurologic complications like Ramsey Hunt, Zoster Ophthalmicus, disseminated zoster require Acyclovir 30mg/kg/day in 3 doses I/V. Oral Acyclovir 80mg/kg/day in 4 divided doses hastens healing. Famciclovir and Foscarnet are drugs used in resistant or recurrent cases.

4. Cytomegalo Virus (CMV)
It is very common OIs and carry poor prognosis. Horizontally transmitted through saliva, sexual fluid, urines and vertically by infected mother. More than 90% of HIV pregnant mother are CMV – infected.
Clinical manifestations:-
a. Retinitis: - Chorioretinitis develops in CMV seropositive cases when CD4 count is < 50 cells/l. Blurred vision, floaters and flashes are nonspecific symptoms, which starts with one eye progressing to other. It is painless. It leads to visual loss and retinal detachment. Yellowish white area of retinal necrosis with perivascular exudates and haemorrhage at periphery is characteristic.
b. GI Manifestation :- Oesophagitis produce substernal pain, dysphagia and anorexia, Colonic involvement cuase diarrhoea, abdominal pain, weight loss , anorexia, fever, CMV hepatitis and gastritis are uncommon. In 5-10% cases of AIDs cause colitis.
c. Penumonitis – Cough, dyspnoea, hypoxaemia
d. Encephalitis – Produce sub-acute dementia complex.
Diagnosis:- Retinitis is diagnosed by Fundoscopy. GIT infections on mucosal biopsy shows inflammation and CMV inclusion bodies. On endoscopy oesophagitis shows small and confluent ulcers. Sigmoidoscopy of colon shows diffuse erythmatic, submucosal haemorrhage and multiple mucosal ulcer. Chest X-ray of pnumonitis shows diffuse interstitial infiltration and finding of inclusion bodies in lung tissues or BAL is supportive.

Serological test for CMV are less helpful.
Treatment: Ganciclovir 10mg/kg/day in 2 divided doses I/V over 2 hours for 14-21 days followed by life long maintenance therapy.
Or
Foscarnet – 180mg/kg/day in 3 divided doses I/V over 1-2 hours for 14-21 days followed by life long maintenance therapy with 90-120mg/kg/IV in a single daily dose.
Prophylaxis :- Regualr retinal examination at 4 – 6 weeks interval. Life long prophylaxis with Ganciclovir 5mg/kg/day IV 5 days per week.

Other viral infections:
1. Human Herpes Virus – 8 (HHV – 8): This DNA virus causes Kaposi sarcoma in seropositive cases. Although Ganciclovir , Foscarnet, Cidofovir are active in vitro their use in limited.
2. Progressive multifocal leukoencephalopathy by JC Virus : This is caused by polyoma Virus JC virus. Insidious onset with progressive features like congnitive dysfunction, dementia, seizure, ataxia, aphasia, cranial nerve palsy, hemiparesis, quadriparesis, Coma. CT scan shows single or multiple hypodense, non-enhancing lesion in cerebral, white matter. Confirmed by biopsy. No effective treatment. Majority dies within 3-6 months of symptoms.
3. Human Papilloma Virus (HPV): - Infection in anogenital tract resulting in transient infection, genital wart, condyloma, squamous cell cancer. Dignosed clinically and biopsy. No effective treatment.
4. Hepatitis C Virus (HCV): - High rate of HCV coinfection in HIV- I persons through drug user injection, mother to child or sexual route. HIV – I infection increases the progress of HCV infection leading to end stage liver disease. Acute HCV infection is symptomatic or mild symptomatic. Chronic infection leads to hepatocellular failure. A progressive form called fibrosing cholestatic hepatitis found in HIV- I infection. Anti viral treatment is considered in chronic HCV infection. Avoid alcohol. Two doses of Hepatitis A vaccination is advised.
5. Hepatitis B Virus (HBV): About 90% of HIV – I patients are +ve for some markers of HBV. It is associated with increased risk of chronic HBV. Symptoms of acute infection are nausea, vomiting, jaundice, abdominal pain, Chronic infection presents as fatigue hepatocellular failure. Testing for HBs Ag, Anti HBc, Anti-HBs are used. Detection of HBs Ag  6 months is chronic and should be tested for HbeAg and Antigen HBe. They are increased risk of carcinoma.
Avoid alcohol – Two doses of Hepatitis A vaccination and 3 doses of Hepatitis B vaccination is given. Antiviral treatment is given.
6. Hepatitis A Virus (HAV) – All susceptible, chronic HCV cases. Two doses of Hepatitis A vaccination given. Not seen so frequently
7. Influenza virus : All patients annually – inactivated trivalent influenca virus vaccine – 1 dose yearly. Oseltamivir – 75 mg orally – 4 tims or Rimantidine /Amantidine – 100 mg orally – 4 times are used.
8. EBV – When CD4 is < 300L cause oral hairy leukoplakia along tongue border and adjacent mucosa. Not a premalignant condition. Treated with topical podophyllin or systemic antiherpes virus infection.
9. Coinfection with hepatitis D, E, and G are also common.

Cryptosporidiosis: Protozoa parasite . Infects small and large gut and extra intestinal. In this group C.hominis (previously C. parvum) C. canis, C. felis, C. muris. C. meleagridis . Biliary tract involvement like papillary stenosis, sclerosing cholangitis are seen.
Microsporidiosis: Protists related to fungus, contains several groups of organism. Water borne in origin. Commonly manifest as diarrhoea. Rarely encephalitis, sinusitis, ocular manifestation, myositis and disseminated infection occur.
Bartonellosis: Bacterial infection causing Bacillary angiomatosis of skin. Organisms are B. henselae, B. quintana and others. Common among poor sanitation. Common when CD4 count is < 50 cells and chronic infection involving every organ but typical skin lesion which is papular, red, smooth surface, vascular and bleed on trauma. Diagnosed by biopsy. Serological test may be +ve before clinical disease. Treated with Erythromycin /Doxycycline/ Clarithromycin/Azithromycin for at least 3 months.
Syphilis: The impact of HIV – I infection on syphillis (Treponema pallidum) pathogenesis, severity , response to treatment and long term sequelae is not well documented. However the progress is hastened in immunocompromised state. A variety of rare presentation like lues maligna, an ulcer due to necrotising vasculitis. Most commonly presented as condylomata lata. VDRL is of ambiguous significance.
FUNGAL INFECTION:
A. Cryptococcal Infection: Cryptococcus neoformans – infects when CD4 count is <50. This unusual disease involves brain, meninges, skin, eye. Clinically may present as meningitis, meningoencephalitis. Pneumonia is seen in 50% of cases. Sepsis though rare is fatal. Post infective sequlae like hydrocephalus, seizure, ataxia, cranial nerve involvement is common. Uncommon presentation may be in skin (Molluscum contagiosum), L. node enlargement, palatal, glossal ulcer, myocarditis, prostitis, gastroenteritis.
In CSF fungus is detected by India ink stain, cryptococcal antigen (95-100% specificity and sensitivity), positive culture. A positive latex agglutination test from seum also used in pulmonary cases. CT Scan of brain may show granuloma (cryptococcomas). Chest X-ray may show poorly localized bronchopneumonia, nodular or lobar involvement, pleural effusion , hilar, mediastinal adenopathy.
Amphotericin B ( 0.5 – 1 mg/kg/day IV , once daily) with or without Flucytosine (50-150 mg/kg/day orally in 4 divided doses) for 14 days until clinical improvement is initial treatment. Fluconazole (6-12 mg/kg/day, orally) or Itraconazole (2-5 mg/kg/day, orally) up to 8-10 weeks is follow up therapy. Life long secondary prophylaxis with Fluconazole or Itraconazole or Amphotericin B is required.
B. Histoplasmosis: Dimorphic fungus Histoplasma capsulatum. By inhalation or reactivation of latent infection. Manifest as disseminated multiorgan disease – fever, fatigue, weight loss, respiratory symptoms. CNS, GIT, Skin Manifestation seen in < 10% of cases. Diagnosed by presence of antigen in serum or urine, fungal stain of blood or tissues. Chest X-ray in 50% show diffuse interstitial infiltration or diffuse nodularity. Bone marrow involvement is common causing anaemia, neutropenia, thrombocytopenia. Treated by Amphotericin-B 1mg/kg/daily followed by Iatraconazole.

C. Coccidioidomycosis: By C. immitis causing disseminated diseases or meningitis. Dissemianted present as generalized lymphadenopathy, skin nodule or ulcer, peritonitis, liver, bone and joint involvement. Local meningitis is 10% of cases. Diagnosed by culture or serology of serum or CSF. Pulmonary (nodules, cavity, pleural effusion, hilar adenopathy) and disseminated form is treated with Amphotericin B and meningitis is treated with Fluconazole.
D. Aspergillosis: By Aspegillus fumigatus causing two syndromes – Respiratory (pseudomembranous tracheitis, penumonitis), CNS infection (meningoencephalitis with vascular infarction). Diagnosed clinically and demonstration of organism. Treated with Amphotericin B or Variconazole.
E. Candida Infection: Oral candidiasis (thrush) and diaper skin are common. Thrush may be extensive. Painless, creamy white plaques over buccal , oropharyngeal, or tongue which can be easily scrapped off. Angular chelosis may be seen. Oesophageal candidiasis may present as substernal or abdominal pain, dysphagia, weight loss. Disseminated infection present as sepsis or shock. Vulvovaginal candidiasis present as creamy to white yellow vaginal discharge with mucosal burning or itching, dysuria, dysparenia. Vaginitis may be due to trichomonas or bacterias also.
Oral candidiasis are typical and confirmed by presence of pesudohyphae on KOH stained specimen. Oesophageal involvement is diagnosed by clinical, endoscopy and biopsy. Blood culture may be +ve.
For oral candidiasis Nystatin, Amphotericin-B and Azoles are used. Oral Azoles are used when topical application fails. For oesophageal candidiasis. Fluconazole and for disseminated Amphotericin B is the choice.
TABLE
Condition Drug Dose & Duration
Oral Candidiases • Nystatin – Suspension, Lozenge
• Amphotericine B oral Suspension
• Clotrimazole
• Fluconazole
• Ketoconazole
• Itraconazole • 1-2 Lak U orally 4 times – 14 day
• 1 mg orally 4 time – 14 day
• 10mg orally 4 times – 14 day
• 3-6 mg/kg orally once – 14 day
• 5-10mg/kg Orally once – 14 day
• 2-5 mg/kg Orally once – 14 day
Esophageal Candidiasis • Fluconazole
• Itraconazole
• Amphotericine – B • As Above
• As Above
• 0.5 – 1 mg/kg/daily IV – 14 days
Disseminated Candidiasis • Amphotericine – B • As Above

Oral Fluconazole is given as prophylaxis is recurrent cases.
E. Other Fungus: Cause meningoencephalitis – Naegleria, Achanthamoeba.

DERMATOLOGIC DISORDERS:
Seborrheic Dermatitis: Seen in 50% of HIV cases. Aggravated by Pityrosporium , a yeast like fungus. Ttopical antifungal treatment is useful.
Eosinophillic pustular folliculitis: Multiple urticarial perifollicualr papules associated with mite infection which respond to topical anthelminthics.
Norwegian scabies: Hyperketatotic psoriasiform lesion.
VZV: Reactivation in 20% cases of HIV, Visceral involvement is rare. Involve several dermatomes Acyclovir, Famciclovir, Foscarnet are used.
HSV: Recurrent oroabial, genital, perianal lesion as part of reactivation. Perirectal is associated with proctotis.
Molluscum Contagiosum: Flesh coloured umbilicated lesion, regress with ARV.
Erythematous Nodules: Due to Atypical microbacteria, fungus, bartonella, Aconthamoeba.

OPHTHALMIC DISEASES:
CMV retinitis: Painless, progressive visual loss with blurred vision. Retina shows perivascualr haemorrhage and exudates.
HSV & VSV: May cause bilateral necrosizing retinitis called Acute Retinal Necrosis Syndrome or Progressive Outer Retinal Necrosis (PORN). There is pain, keratitis, iritis , associated with orolabial HSV or trigeminal zoaster. Fundus shows pale gray periphery. Complicated by retinal detachment.
Other infections: P. carinii- Choroid lesion- Bilateral elevated yellow white plaque. Toxoplasma – Chorioretinitis associated with CNS lesion.

RECURRENT BACTERIAL INFECTIONS:
Recurrent bacterial infections within 2 years period is peculiar to HIV patients. The clinical presentation depends on the system involved.

TABLE
Site of infection Common Organism Clinical Manifestation Diagnostic Evaluation
Meningitis S. penumonia
H. influenzae
N. meningitides Fever, Headache, Vomiting, Altered sensorium, Neck rigidity CSF – examination and culture
Pneumonia S. penumonia
H. influenzae
Ps.aeruginosa
N. aosteroides Fever, cough, chest pain, tachypnea, crepitation Chest X-ray, Sputum Culture
Bacteremia S. penumonia
H. influenzae
Salmonella species Fever Or Hypothermia , Features of Multiorgan Dysfucntion Blood Culture
Oesteomyelitis Staphylococci Fever, pain, swelling or redness at local site Bone scan, Radiograph
Sinusitis S. penumonia
H. influenzae Persistent nasal discharge , fever, cough, Maxillary sinus – common Radiograph
Central venous catheter infection Staph aureus & epidermidis.
K. penumonae
Acinetonbacter species
Pseudomonas Species Redness and tenderness at local site Culture
Skin, ear and upper respiratory tract S. penumonia
H. influenzae
Group A beta fever, Haemolytic URTI Skin- Pyoderma
Ear- Pain, Discharge
URTI- Cough Culture from specimen

Treatment depends on culture sensitivity. Empiric broad spectrum antibiotic may be started taking into account the site of infection, nuetropenia, in dwelling catheter and other risk factors.

For prophylaxis immunization against organism and proper hygiene is to be maintained. Daily TMP-SMX may be used. Intervenous immunoglobulin monthly may boost the immunity.


DIARRHOEA:
Chronic diarrhoea is very common, which may be due to various organisms and side effects of drugs.
TABLE
Organism Species
Bacteria Salmonella, Shigella, Campylobacter, Clostridium difficile & MAC
Virus CMV, Adenovirus, HIV, HSV, Rota Virus
Protozoa Isopora belli, Cryptosporidium parvum, Microsporidia, E. histolytica, G. lamblia, Cyclospora
Fungi Histoplasma, Coccidiodomycosis, Penicilliosis

Peritonitis is seen in C.immitis.
Clinically presents as large watery stool, abdominal pain associated with fever, dehydration, anorexia, wasting and cachexia. Biliary tract involvement (cholangitis, cholecystitis) is seen in Isospora, Microsporidium, Cryptosporidium and Cyclospora.

DIAGNOSIS AND TREATMENT
Organism Diagnosis Treatment
Isospora Oocyst in stool after acid fast stain TMP SMX – 3-4 weeks Pyrimethamine with folinic acid
Cyclospora Oocyst in stool in acid fast stain Orally TMP SMX for 7 days
Microsporidia
Examiantion of concentrated stool,small intestine biopsy on EM or PCR Albendazole
Cryptosporidium
Stool examination in acid fast stain, Immunoflucoscent assay and stool ELISA Fluid supplementation, Paramomycin- Spiramycin, Azithromycin, Clarithromycin
E. histolytica Stool , trophozoite & Cyst, Serological test - +ve with tissue invasion, Endoscopy and biopsy For gut – Iodoquinol, diloxanide furoate, paramomycin
Invasive – Metronidazole, Dehydrometine
Hepatic – Chloroquine
G. lamblia Trophozoite and cyst in stool or duodenal aspirate, Giardia antigen in stool Metronidazole, Furazolidine, Tinidazole
Adenovirus Sigmoidoscopy – Patchy erythema & raised white lesion
Mucosal Biopsy – Intranuclear inclusion , Virus may grow Supportive treatment
Rotavirus ELISA in stool sample Supportive treatment
Camphylobacter Stool culture or blood culture.
Immunological test – IF, LA
Serology – ELISA for IgG, IgM, IgA level Azithromycin, Clarithromycin, Erythromycin, Ciporfloxacin, supportive therapy
Shigella Endoscopy – Deep mucosal ulcer and pseudomembrane
Stool Culture Ampicillin , cefixime, ceftriazone, Quinolones, Supportive care
Salmonella Stool Culture
LA and Fluorescence test
PCR Duration of treatment is 14 days
Cefotaxime /Ceftriaxone, Ciprofloxacin
Cl. difficile Stool Examination
Toxins detected by ELISA Supportive
Metronidazole
Vancomycin

Special Geographical OIs:
1. Penicilliosis: By dimorphic fungus Penicillium marneffei seen in Thailand, China. Infect when CD4 is less than 50 and high mortality if untreated. Presents as fever, weight loss, with skin, lymph node, bone marrow and hepatic involvement. Cutaneous lesions are papullar with central umbilication over face, ears and extremities. Fungus can be demonstrated. Treated with Amphotericin B for 2 weeks followed by Itraconazole for 10 weeks.
2. Leishmaniasis: It is an obligatory intracellular protozoa seen worldwide. May present as localized or diffuse cutaneous, mucosal or visceral disease, the last being common in AIDS (70%). Demonstration of Leishmania from lesion and antibody is diagnostic. Treated with pentavalent antimony.
3. Paracoccidiodomycosis: Dimorphic fungus P. brasiliensis, seen in central and South American. Few cases in HIV – I presenting multisystemic involvement. Treated with Amphotericin B or Azoles.
4. Isosporiasis: the Protozoa I.belli present in Caribbean & Africa and Worldwide. Presents as diarrhoea with systemic symptoms of fever, weight loss, abdominal pain. Treatment is supportive. Pyrimethamine or TMP-SMX are tried.
5. Chaga’s disease (American Trypanosomiasis): A flagellated protozoa T. cruzi. Among HIV-I infected persons with immunosuppression the reactivation is increased. Present as fever, headache, vomiting, seizure. Single or multiple ring enhancement in subcortical area (Vs toxoplasma – deeper). CSF may show increased cell and proteins. Organism found in blood or tissue. Treated with Benzimidazole (2.5 mg/kg BID) or Nifurtimox ( 2 mg/kg/QID) for 60 days followed by maintenance therapy for life with either drug in a dose of 5 mg /kg thrice a week.
6. Microsporidia: Small unicellular, obligate intracellular parasite, reside in the cytoplasm of enteric cells. The main species is Enterocytozoon bieneusi. Detected by light microscope with chromotobe bases stain. E/M of stain. In contrast to cryptococcal it is seen in other tissue like eye, muscle, liver . Albendazole is treatment.
7. Cryptosporidia: Symptoms range from self limiting, intermittent to sever life threatening diarrhoea. Assoiciated with nausea, vomiting, crampy abdominal pain. Associated with cholangitis and cholecystitis. Diarrhoea is non-inflammatory. Stool containing occyst stain with acid fast.

SUMMARY
• Opportunistic infections due to various organism are associated with HIV infection at some stage or other.
• They can be classified depending on the CD4 count or system involved.
• PCP is commonest form of pneumonia though there is a six-fold rise of pneumonia incidence due to other bacterias.
• The incidence, complications and resistance of M. tuberculosis is more in HIV cases. ATT is modified according to immune status of the patient.
• Atypical mycobacteria specially MAC incidence is common.
• Toxoplasma gondii infection of CNS leads to various clinical presentation.
• The common viral infections are HSV, CMV, VZV, EBV, HBV and HCV. CMV products commonly retinitis and GI complications.
• Fungal infections like candida, cryptococcal and histoplasma are common producing various complications.
• Dermatological and Ophthalmic complication due to various infections are vary often encountered.
• Due to low immune status recurrent bacterial infections give rise to varied clinical manifestations.
• Chronic diarrhoea due to multiple microogransim is a constant problem.
• Depending on the geographical distribution of some organism the infection predominantly seen.

CONCLUSION

With high prevalence of AIDS in developing and underdeveloped Countries the risk of OIs due to organisms is a menance. The clinical presentations are quite different than normal host. Wherever possible attempts are to be made to obtain tissue or specimen to establish a definitive diagnosis. Various studies have proved the relation between CD4 count and progression of HIV and OIs. Timely diagnosis and treatment and chemoprophylaxis have reduced the mortality and morbidity. Additional ART successfully decreases the organism load and restores the immune function reducing the development of OIs.

CLINICAL FOCUS
• OIs due to various microorganism go hand in hand with infection.
• The clinical presentation somewhat differ from normal host.
• Depending of CD4 count the HIV related infections are different.
• PCP is commonest infection in children and adult having high fatality if untreated.
• Depressing cellular immunity is responsible for high incidence of tubercular infection where the treatment modality depends on CD4 count.
• Atypical mycobacteria specially MAC is quite common giving rise to various systemic complications.
• Toxoplasma infection is another treatable neurological infection.
• Various viral infections are common out of which CMV carry poor prognosis as it involves multisystems.
• EBV produces hairycell leukoplakia.
• Incidence of HBV is about 90% of HIV cases,
• Fungal infections like Cryptococcus, Histoplasma present as disseminated multiorgan disease.
• Oral, oesophageal and vulvovaginal candidiasis are common and can be properly treated.
• CMV retinitis causes progressive permanent blindness.
• Recurrent bacterial infections are common giving rise tp various diseases.
• Chronic diarrhoea is very common, due to organism or drugs.