INFECTIOUS DISEASES I.pptx

INFECTIOUS DISEASES I HIV INFECTION IN CHILDREN DR UGOLEE JERRY DEFINATION OF TERMS • HIV Retesting : a second HIV test conducted after the first positive result. Recommended before initiation of ART. • HTS: HIV testing services. • ART: Anti retroviral therapy- the use of 3 or more ARV’s in orde...

INFECTIOUS DISEASES I HIV INFECTION IN CHILDREN DR UGOLEE JERRY DEFINATION OF TERMS • HIV Retesting : a second HIV test conducted after the first positive result. Recommended before initiation of ART. • HTS: HIV testing services. • ART: Anti retroviral therapy- the use of 3 or more ARV’s in order to achieve better viral suppression. The terms Highly active anti-retroviral therapy (HAART) or combination Anti-Retroviral Therapy(cART) may be used for it interchangeably. • PMTCT: prevention of mother-child transmission. Includes strategies for ensuring that HIV infection is not transmitted during pregnancy and lactation periods DEFINATION OF TERMS • EID: early infant diagnosis refers to testing all HIV exposed babies to determine their true HIV status by detecting the presence of HIV DNA using PCR. • PrEP: Pre- exposure prophylaxis is when people at very high risk for HIV infection take oral ART to reduces the chances of becoming infected e.g discordant couple. • PEP; post exposure prophylaxis is the use of oral ART after exposure to block acquisition of HIV infection e.g rape victims. • CPT: cotrimoxazole preventive therapy is the use of cotrimoxazole in all HIV positive patients to prevent the development of a variety of infections including PJP. INTRODUCTION • HIV infection is a major cause of infant and childhood mortality and morbidity in Africa. • In 1982 the first paediatric case of HIV/AIDS was reported. • In Nigeria in 1986, the first reported case of HIV/AIDS was a 13 year old female hawker in Calabar, Cross Rivers state. INTRODUCTION • Each day 1,500 children under the age of 15years become infected with HIV infection worldwide. Ninety percent of them are resident in sub-Saharan Africa. • While HIV infection rate steadily declines in most developed countries, as at 2019, 1.8million of the 36.9million people living with HIV lived in Nigeria making her the country with the fourth-largest HIV epidemic in the world. Amongst these numbers, 220 thousand were children (0-19years). • Worldwide, AIDS is responsible for 3% of deaths, and 6% in sub-Sahara Africa. In Nigeria 150,000 deaths occurred in 2017 from HIV/AIDS related illnesses. INTRODUCTION • One in every seven persons dying from HIV related illness worldwide, is a child under 15years,largely due to a failure to introduce programs for PMTCT on a scale that is needed. Only 36% of children eligible for ART in Nigeria are receiving it. • Without care, including ART, the progression of HIV infection is often aggressive especially in children. Yet paediatric HIV is almost entirely preventable as it has been virtually eliminated in high income countries with MTCT rates lower than 2%. • Intercurrent infections, malnutrition, delayed definitive diagnosis and lack of access to primary HIV care all result in a higher mortality rate amongst HIV infected children in Nigeria. INTRODUCTION •At birth viral load is usually very low but increases within the first 2months of life, thereafter it remains high until age 23years then it declines to a set point stemming largely from the lower efficiency of a child’s immature lymphatic immune system to mount a HIV-specific response. •Prenatally infected children fall into one of three category 1.Rapid Progressor's – develop signs and die by 1year(25-30%) 2.Develop signs early in life, followed by rapid deterioration, die by 3-5years(50-60%). 3.Long term survivors may live beyond 8years (5-23%). AETIOLOGY • Human Immunodeficiency Viruses types 1 • • • • and 2. RNA viruses Both are members of the lentivirus genus and retroviridae family. HIV type 1 occurs worldwide. HIV 2 is less prevalent and occurs principally in West Africa . AETIOLOGY • The mature genome of HIV is diploid with 2 identical single-stranded RNA copies. • The genome includes three major regions important in viral replication namely: GAG, POL and ENV • The ENV region encodes for the viral envelope AETIOLOGY • The GAG gene encodes for the viral core proteins (p24, p17, p9 and p6) which are derived from the precursor protein p55 • POL gene encodes the viral enzymes  reverse transcriptase (p51)  protease (p10), and  integrase (p32) AETIOLOGY PATHOPHYSIOLOY • The HIV primarily targets CD4+ molecule on T-helper cells. • Other target cells include macrophages and glial cells. • The virus is able to infect host cells via several steps: - binding, fusion, entry, reverse transcription, integration and replication, assembling, budding and maturation. PATHOPHYSIOLOY • CD4+ cells play vital roles in humoral and cell-mediated immunity • Continuous CD4+ loss leads to progressive immunosuppression and increase the incidence of opportunistic infections (OIs) • CD4+ cells eventually become overwhelmed and the immune system fails to cope with opportunistic infections, leading to progression to AIDS. MODE OF TRANSMISSION • Vertical transmission/Maternal to child transmission (MTCT) • Horizontal transmission MODE OF TRANSMISSION • Vertical transmission/Maternal to child transmission (MTCT) is the predominant route of transmission in children • Accounts for >90% of cases • Could occur In-utero Intrapartum (during delivery) Postpartum (via breastfeeding) MODE OF TRANSMISSION • Horizontal transmission occurs via: • Unprotected sexual intercourse • Transfusion of infected blood/ blood products • Use of infected sharps like needles MODE OF TRANSMISSION •FACTORS ASSOCIATED WITH INCREASED MTCT include •High maternal viral load •Low CD4+ count •Lack of HIV neutralizing antibodies •Advanced clinical disease •First born twins •Preterm delivery (<34 weeks GA) MODE OF TRANSMISSION •Obstetric factors: chorioamnionitis, mode of delivery (vaginal > CS), >4hours duration of rupture of membrane •Birth weight < 2.5kg •Breastfeeding CLINICAL FEATURES •Clinical manifestations are usually due to infections by other organisms as a result of the immunosuppression caused by HIV. Can affect any organ system: •Respiratory system: PTB Lymphocytic Interstitial Pneumonia (LIP) Pneumonia (commonly due to PJP) Bronchiectasis Otitis media & Sinusitis( due to S.pneumonia, H. influenza) CLINICAL FEATURES • • • • • • CVS: Dilated cardiomyopathy Left ventricular hypertrophy CCF Marked sinus arrhythmia Resting sinus tachycardia CLINICAL FEATURES • Digestive system: • Oral manifestations: oral/oropharyngeal candidiasis, ulcerative gingivitis, oral hairy leukoplakia • Chronic or recurrent diarrhea • Abdominal pain • Failure to thrive CLINICAL FEATURES •Urogenital system: •Nephrotic syndrome •HIVAN •Delayed Puberty •Hematologic system: •Anaemia 20 poor nutrition, chronic infection, drugs eg Zidovudine •Leukopenia •Thrombocytopenia CLINICAL FEATURES •CNS •Developmental delay •HIV encephalopathy-progressive encephalopathy with loss or plateau of developmental milestones and acquired microcephally •Cognitive deterioration •Symmetric motor dysfunction OPPORTUNISTIC INFECTIONS (OIs) • Are infections caused by organisms which in the immune competent host will not cause significant disease • Fungal Ois- oral and oesophageal Candidiasis, Dermatophytoses (e.g. Tinea capitis, corporis), Pneumocystis jirovecii (carinii) pneumonia, Cryptococcal meningitis. • Bacterial Ois-Tuberculosis and other mycobacterial infections, Pyogenic infections (e.g. pneumonia, soft tissue and skin infections OPPORTUNISTIC INFECTIONS (OIs) Viral causes Herpes simplex infections, Cytomegalovirus infections, Human papilloma virus infection (e.g. Verruca plana, genital warts), Lymphoid interstitial pneumonitis. •Protozoan and Parasitic causes –Toxoplasmasis (T. gondii)Cryptosporidiosis, Malaria, Scabies • CLASSIFICATION There are 2 international classification systems for HIV disease: WHO classification system CDC classification system • •These systems classify HIV disease based on immunological and clinical criteria CLASSIFICATION • WHO CLINICAL STAGE 1 • Asymptomatic • Persistent generalized lymphadenopathy WHO CLINICAL STAGE 2 • • • • Hepatosplenomegaly Papular puritic eruptions Seborrhoeic dermatitis Extensive human papilloma virus infection • Extensive molluscum contagiosum • Fungal nail infections • Recurrent oral ulcerations • Lineal gingival erythema (LGE) • Angular cheilitis • Parotid enlargement • Herpes zoster • Recurrent or chronic RTIs (otitis media, otorrhoea, sinusitis) WHO CLINICAL STAGE 3 • Moderate unexplained malnutrition not adequately responding to standard therapy • Unexplained persistent diarrhea (14 days or more) • Unexplained persistent fever (intermittent or constant, for longer than one month) • Oral candidiasis (outside neonatal period) • Oral hairy leukoplakia • Acute necrotizing ulcerative gingivitis/periodontitis • Pulmonary TB • Severe recurrent presumed bacterial pneumonia • Chronic HIVassociated lung disease including bronchiectasis • Lymphoid interstitial pneumonitis (LIP) • Unexplained anaemia (<8g/dl), and or neutropenia (<1000/mm3) and or thrombocytopenia (<50000/mm3) for more than one month WHO CLINICAL STAGE 4 • Conditions where a presumptive diagnosis can be made on the basis of clinical signs or simple investigations • Unexplained severe wasting or severe malnutrition not adequately responding to standard therapy • Pneumocystis pneumonia • Recurrent severe presumed bacterial infections (e.g. empyema, pyomyositis, bone or joint infection, meningitis, but excluding pneumonia) • Chronic herpes simplex infection; (orolabial or cutaneous of more than one month’s duration) • Extrapulmonary TB • Kaposi’s sarcoma • Oesophageal candidiasis • CNS toxoplasmosis (outside the neonatal period) • HIV encephalopathy CLASSIFICATION • • • • • • • • WHO CLINICAL STAGE 4 CMV infection Extrapulmonary cryptococcosis including meningitis Cryptosporidiosis Isosporiasis Cerebral or B cell non-Hodgkin lymphoma Progressive multifocal leukoencephalopathy (PML) HIV-associated cardiomyopathy or HIV- associated nephropathy DIAGNOSIS • HIV diagnosis is basically providing proof of the presence of HIV infection in a child. • May be done by demonstrating the presence of HIV antibodies in plasma or serum (indirect) or the virus in blood(direct). • The antibody test is a suitable for diagnosis in adults and children above 18months. Nucleic acid tests are used mainly for diagnosis in children less than 18months. • HIV testing services( HTS) remains the gateway to HIV prevention and control, it includes services that provide diagnosis, testing methods, counselling and linkage to treatment plus other support services. DIAGNOSIS • All forms of HIV testing should be voluntary and should adhere to WHO’s 5 C’s( Consent, Confidentiality, Counselling, Correct test results and Connection to care, treatment and prevention services). • HTS may be offered in a healthcare facility or community following different delivery models, these include; • Facility based model where HTS is routinely offered to all patients, may incorporate both client-initiated and/or provider-initiated approaches. • Client-initiated approach- individuals volunteer for counselling and testing. DIAGNOSIS • Provider-initiated testing and counselling(PITC) allows healthcare providers to recommend HTS routinely to parents/clients as a standard component of medical care provided in the facility. May take the opt-in or opt-out approach. • In the opt-out model HTS is provided to every patient and he/she is informed of their right to refuse testing. • In the opt-in model, HTS is recommended to all patients and their explicit consent is required prior to testing. • Community based HTS refers to offering HIV testing to schools, work places, churches, bars and other public places in tents or mobile cars LABORATORY DIAGNOSIS • Current available technology allows for HIV antibodies to be detected as early as 4-6weeks of the infection and by 24weeks in virtually all infected individuals. Antibodies develop 1-3 months after the initial infection (WINDOW PERIOD) • There are two commonly used testing algorithms, the serial and parallel testing algorithms. • In serial testing, two different antibody screening tests are employed sequentially. If the initial screen is negative, no further testing is required. If positive second antibody test(more specific &less sensitive than the first)is done. LABORATORY DIAGNOSIS In Parallel testing: •Two different RDT are used AT THE SAME TIME •A positive result in both tests indicates HIV infection •A discordant result will require the use of a third and entirely different RDT (Tie breaker). •Has the advantage of reduced test time and reduced incidence of false negative results. •The nucleic acid based tests are expensive and require expertise thus are not done routinely, they include DNA PCR, reverse transcriptase PCR, P24 antigen and viral culture all of which detect viral particles in blood. LABORATORY DIAGNOSIS Screening test: •Rapid diagnostic test (RDT) or ELISA •Examples: Determine, Unigold, Stat-pack RDT kits •Other available antibody kits include the double-check gold and sure-check, any of which may be used as a third test(tie breaker) when the initial two results are discordant. Confirmatory test: •Western blot and indirect immunofluorescent assay •Done to rule out false positive screening test LABORATORY DIAGNOSIS •It is recommended that HIV-exposed babies have an initial DNA PCR at 4-6weeks of age and after 12weeks after complete cessation of breastfeeding. •Children between 9-18months at first presentation should first have a rapid test done, if positive, a DNA PCR test should be done to confirm infection. •Children ˃18months should have an antibody detection test done and if positive commenced on ART. If negative and breastfeeding. a repeat antibody test should be done 12weeks after complete cessation of breastfeeding. •Seriously sick children <18months in whom HIV infection is suspected, in the absence of nucleic acid testing should have a rapid test and be staged for presumptive clinical diagnosis. If staged as advanced or severe(WHO 3&4) may commence ART. LABORATORY DIAGNOSIS Ancillary investigations done following diagnosis and prior to initiation of treatment include: • FBC • CD4+ count • Viral load • LFT • HBV and HCV assays • SEUCr • CXR • Gene Xpert or Mantoux test TREATMENT •Following a diagnosis of HIV infection, a package of support interventions geared at providing enhanced treatment and follow up care should be offered to all children. •ART is the use of a combination of anti-retroviral drugs to treat HIV infection with the goal of achieving sustained virologic, immunologic and clinical control of the infection. •Current guidelines for HIV prevention, treatment and care recommends that ART be initiated in all adolescents, pregnant and breastfeeding women and children with confirmed diagnosis irrespective of WHO clinical stage or CD4 count. TREATMENT ELIGIBILITY FOR ART • Every HIV-infected child is eligible for ART regardless of age, WHO clinical stage or CD4+ cell count TREATMENT • All who are to be initiated on ART however must be willing and ready to adhere to drug regimen and must understand that treatment is lifelong. • Adherence refers to a partnership between the patient, family and health care team to ensure that medication is taken exactly as prescribed • It implies that parent/care giver accepts active role in care (as opposed to compliance which implies lack of shared decision making) TREATMENT • Adherence >95% to ART ensures good virologic response (prevents resistance), e.g for a child on b.d medication, omitting >1 dose in 10 days implies <95% adherence • FACTORS THAT AFFECT ART ADHERENCE 1. Health care provider related factors: • Communication skills • Quality of counselling • Experience in HIV treatment • Adherence team support TREATMENT 2. Patient-related factors • HIV/AIDS knowledge • Readiness & commitment to treatment • Dependence on caregiver • Refusal of child • Lack of routine • Change of caretaker • School/daycare • Reluctance to disclose child’s disease to others decreases social support • Stigma • Cultural beliefs • Psychological issues e.g depression FACTORS THAT AFFECT ART ADHERENCE 3. Treatment regimen related factors • Pill burden • Frequency of administration • Side effects, drug interaction • Poor palatibility 4. Clinical Environment • Distance to facility • Clinic staff attitude • Cost of treatment TREATMENT • All who are to be initiated on ART however must be willing and ready to adhere to drug regimen and must understand that treatment is lifelong. • Priority should be given to initiating ART’s in 1. Adolescents with advanced or severe clinical disease (stage3&4) with CD4 count <350cells/mmᶾ 2. All children older than 5years with WHO stage 3&4disease or CD4 cell count <350cells/mmᶾ 3. All HIV positive children less than 2years of age 4. All children <5years with CD4 cell count <750cells/mmᶾ TREATMENT •Highly active antiretroviral therapy (HAART) is the standard treatment for HIV infection. It is the combination of a minimum of three drugs from at least two different classes of ARV drugs. •When optimal, the administration of ART should lead to a suppression of viral load to ≤400copies/ml after 24weeks of initiation and a progressive increase in CD4 cell count at a rate of 50100cells/μl/year. •Clinically, it should result in reduced morbidity from opportunistic infections and reduced reoccurrences of intercurrent infections. •ART’s are classified based on their various modes of antiviral actions with each drug targeting a different step in the viral life cycle. TREATMENT •Nucleoside Reverse Transcriptase Inhibitors(NRIT’s)- compete with host nucleotides to serve as substrates for reverse transcriptase chain elongation, resulting in chain termination. Examples Lamivudine(3Tc), Zidovudine(AZT), Abacavir (ABC), Tenofovir(TDF). • Non Nucleotide Reverse Transcriptase Inhibitors (NNRTI’s) – inhibit HIV reverse transcriptase by binding a hydrophobic pocket close to its active site thus locking the site, e.g Nevirapine (NVP), Efavirenz (EFV) •Protease Inhibitors(PI) – inhibit HIV protease by binding to its active site, examples include Ritonavir (RTV), Daranavir(DRV), Raltogravir(RAL) TREATMENT • HIV intergrase Inhibitors – inhibit DNA strand transfer into host cell genome, e.g Dolutegravir(DTG), Elvitegravir(EVG), Raltegravir (RAL) • Others are Entry inhibitors and Pharmacokinetic enhancers TREATMENT • Commonly 2 NRTI’s and 1 NNRTI OR 1 PI is used Preferred First line combinations: • In neonates: ZDV + 3TC + RAL • In young children: ABC + 3TC + DTG • In adolescents: TDF + 3TC + DTG TREATMENT •Safety, tolerability, efficacy and favourable pharmacokinetics of DTG for children <6years have not been demonstrated in the long term. A Raltegravira(RAL)-based regimen is thus recommended as an alternative 1st line regimen for neonates, infants and younger children •When the currently recommended first line drugs are unavailable, commonly used first line drug alternatives are: •AZT + 3TC + NVP Or TDF + 3TC + EFV- for infected adolescents. •ABC +3TC +NVP Or AZT +3TC +NVP- for children 3-10years of age. •ABC + 3TC +LPV/r Or AZT + 3TC + NVP – for children <3years. COMMON SIDE EFFECTS OF ART’S DRUG CLASS DRUG ABNORMALITY LAB TESTS NRTI ZIDOVUDINE Anaemia, leukopenia, neutropenia FBC, CPK (Creatinine phosphokinase) ABACAVIR Hepatoxicity, hypersensitivity Liver enzymes, CPK TENOFOVIR Renal toxicity Creatinine, urinalysis EMTRICITABINE Hepatotoxicity Liver enzymes DRUG CLASS DRUG ABNORMALITY LAB TESTS COMMON ADR & TOXICITY OF ARV NNRTI PI EFAVIRENZ Hepatotoxicity Liver enzymes Hypercholestero Serum lemia cholesterol Persistent CNS toxicity NEVIRAPINE Hepatotoxicity Stevens Johnson syndrome DRESS Syndrome(drug rash,eosinophili a &systemic symptoms) Liver enzymes RITONAVIR Hepatotoxicity Hyperglycemia hyperlipidemia Liver enzymes Urinalysis,RBS Serum lipids CPK, Uric acid LOPINAVIR/ RITONAVIR Hepatoxicity Pancreatitis Arrythmias Dyslipidaemia Liver enzymes Serum amylase ECG Lipid profile TREATMENT • ART treatment failure may be described as virologic, immunologic or clinical for children. • Clinical failure refers to the occurrence of new or recurrent clinical events indicating advanced or severe immunodeficiency (WHO stage 3&4), with the exception of TB, after 6months of adherent ARV’s. • Immunologic failure refers to persistent CD4⁺ cell count below 200cells/mmᶾ or <10% in children <5years OR 100cells/mmᶾ in children ˃5years after 6months of adherent therapy. • Virologic failure refers to plasma viral load above 1000copies/ml following two consecutive measurements despite adherent therapy Immune Reconstitution Inflammatory Syndrome(IRIS) • Is a paradoxical clinical deterioration after starting ART, due to improving immunity interacting with organisms that have colonized the body at early stages of HIV infection • In spite of the clinical deterioration, there is improvement in CD4+ counts & suppression of viral load • Characterized by onset of new systemic features, may occur during the first 3 months of ART.Is generally self-limiting & lasts 10-40 days • The most common opportunistic infection (OI) associated with IRIS is TB Immune Reconstitution Inflammatory Syndrome(IRIS) TREATMENT OF IRIS • Do not interrupt ART treatment • NSAIDS • Short course Prednisolone (1-2mg/kg/day for 4-6weeks) for severe cases PREVENTION OF IRIS • Commence anti-koch’s for about 2 weeks before commencing HAART CARE AND SUPPORT • Care for the HIV exposed new born and infant begins during resuscitation following delivery and includes ARV prophylaxis, Cotimoxazole prophylaxis, determining an appropriate infant feeding option and immunization. • At birth the HIV exposed should have its mouth and nostrils wiped with gauze at the delivery of the head. The cord should be clamped immediately without milking it and baby cleaned with warm chlorhexidine. • All HIV exposed infants should receive ARV prophylaxis(NVP once daily X 6weeks)from within 72hrs and those born to high risk mothers should receive dual prophylaxis with AZT(twice daily) & NVP(once daily) for the first 12weeks of life. High risk infants include those born to mothers with incident HIV infection during delivery or who received<4weeks of ARV. CARE AND SUPPORT • Cotrimoxazole preventive therapy(CPT) is the use of sulfamethoxazole & trimethoprim fixed-dose combinations to prevent some AIDS-associated opportunistic diseases like PJP and toxoplasmosis as well as in the treatment of a variety of bacterial and protozoan infections. • CPT is recommended for infants, children and adolescents with HIV irrespective of their clinical or immune status. For infants <6monts (120mg once daily), children 6months- 5years(240mg once daily),6years–14years(480mg once daily), ˃14years (960mg once daily). CARE AND SUPPORT • Immunization  HIV exposed children (children whose status are unknown but were born to HIV-infected mothers ) should receive all vaccines according to NPI schedule  Asymptomatic HIV infected children (WHO Clinical Stages 1 and 2) should receive ALL vaccines according to NPI schedule  Symptomatic children (WHO Clinical Stages 3 and 4) should not be given live vaccines: BCG, OPV, measles, Yellow fever vaccines. CARE AND SUPPORT Infant feeding options For mothers who choose to breast feed: • Exclusively breastfeed for the first 6 months of life • Commence complementary feeds at 6 months while continuing breastfeeding for up to 1 year • Avoid mixed feeding (in the first 6 months of life) • The alternative feeding option is infant formula use, under conditions that must be AFASS (Acceptable, Sustainable, Feasible, Safe, Affordable) • Wet nursing by a HIV negative woman CARE AND SUPPORT • Orphans and Vulnerable Children (OVC) care,Psychosocial support, Education and vocational training PREVENTION OF HIV • Adopting the “ABCDE” approach: A- Abstinence from sexual intercourse B- Being faithful to one’s partner C- Condom use correctly & consistently D- Delaying sexual debut for youths E- Examining self (know your status)