HIV Malaria+Tropical Diseases

8/8/2019 HIV Malaria+Tropical Diseases

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1ASHM International short course 2007: HV + Tro ical infections. Sarah Huffam

HIV and Tropical Diseases

ASHM International Short Course 2007

Sarah HuffamInfectious Diseases and Sexual Health Physician

National Centre in HIV Epidemiology and Clinical Research, UNSW Australia

Seconded to the National Centre for HIV/AIDS Dermatology and STI, Phnom Penh, Cambodia
http://images.google.com/imgres?imgurl=http://www.waterencyclopedia.com/images/wsci_03_img0396.jpg&imgrefurl=http://www.waterencyclopedia.com/Oc-Po/Oceans-Tropical.html&h=229&w=335&sz=14&hl=en&start=1&tbnid=rMp3xfnD5DrF9M:&tbnh=81&tbnw=119&prev=/images%3Fq%3Dtropical%2Bpalm%2Btree%26gbv%3D2%26svnum%3D10%26hl%3Den


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10 Leading Causes of Death + Burden of Disease

in Low and Middle Income Countries, by Region, 2001

East Asia and Pacific % of total

DALYs

1 Cerebrovascular disease 7.5

2 Perinatal conditions 5.4

3 Chronic obstructive

pulmonary disease

5.0

4 Ischemic heart disease 4.1

5 Unipolar depressive disorders 4.1

6 Tuberculosis 3.1

7 Lower respiratory infections 3.1

8 Road traffic accidents 3.0

9 Cataracts 2.8

10 Diarrheal diseases 2.5

East Asia and Pacific % of total

deaths

1 Cerebrovascular disease 14.62 Chronic obstructive

pulmonary disease

10.8

3 Ischemic heart disease 8.8

4 Lower respiratory infections 4.2

5 Tuberculosis 4.1

6 Perinatal conditions 3.8

7 Stomach cancer 3.4

8 Lower respiratory cancers 3.0

9 Liver cancer 2.9

10 Road traffic accidents 2.8

http://www.dcp2.org/pubs/GBD/3/Table/3.16


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Non communicable diseases:

relationship with HIV Impact of metabolic complications of HIV and

ART on cardiovascular risk. importance of assessment and management of

modifiable risk factors (smoking, HT, lipids, diabetes,

diet, exercise etc)

Depressive disorders impact on adherence toHIV medication, and prevention of transmission

importance ofassessment and management of depression,and other mental illness


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ASHM International short course 2007: HV + Tro ical infections. Sarah Huffam

Worldwide infectious disease mortality

Six diseases 90 % of deaths attributed to infections:

pneumonia tuberculosis

diarrhoeal diseases

malaria measles

HIV/AIDS

Other tropical infections significant morbidity + mortality:

leishmaniasis, schistosomiasis, filariasis, onchocerciasis,leprosy


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WHO Staging HIV Infection in Adults and Adolescents (red text = infectious agents common in tropics )

Clinical Stage II: Weight loss, < 10 % of body weight.

Minor mucocutaneous manifestations (seborrheic dermatitis, prurigo, fungal nail infections, recurrent oralulcerations, angular cheilitis).

Herpes Zoster, within the last 5 years.

Recurrent upper respiratory tract infections (i.e., bacterial sinusitis).

Clinical Stage III:

Weight loss, > 10 % of body weight.

Unexplained chronic diarrhoea, > 1 month.

Unexplained prolonged fever (intermittent or constant), > 1 month.

Oral candidiasis (thrush).

Oral hairy leukoplakia.

Pulmonary tuberculosis, within the past year.

Severe bacterial infections (i.e., pneumonia, pyomyositis).

Clinical Stage IV:

HIV wasting syndrome, as defined by CDC1. Pneumocystis carinii pneumonia.

Toxoplasmosis of the brain.

Cryptosporidiosis with diarrhoea, > 1 month.

Cryptococcosis, extrapulmonary.

Cytomegalovirus (CMV) disease of an organ other than liver, spleen or lymph nodes.

Herpes simplex virus (HSV) infection, mucocutaneous > 1 month, or visceral any duration. Progressive multifocal leukoencephalopathy (PML).

Any disseminated endemic mycosis (i.e. histoplasmosis, coccidioidomycosis).

Candidiasis of the oesophagus, trachea, bronchi or lungs.

Atypical mycobacteriosis, disseminated.

Non-typhoid Salmonella septicaemia.

Extrapulmonary tuberculosis.

Lymphoma. Kaposis sarcoma (KS).

HIV encephalopathy, as defined by CDC2.


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Case study

23 year old married woman

Lives in a highly malaria endemic area, which also has amoderate prevalence of HIV

Presents with 3 day history of fever, chills, (no rigors)

mild myalgia and headache

Gravida 3 Para 2, LNMP 8 weeks ago

O/E conjunctival pallor, spleen 1cm below costal margin,

liver span 14cm Assessment?

Investigations? + Management?



HIV : Malaria

prevalence distributions

World Health Organization, Malaria and HIV interactions and their implications for public health policy. Report of a Technical Consultation Geneva, Switzerland,23-25 June 2004



Referencehttp://www.who.int/malaria



HIV : malaria co infection

impact on transmission

Most important interaction is HIV: Plasmodium falciparum

Does HIV malaria transmission?

HIV susceptibility to malaria infection

Higher levels of parasitaemia (gametocytes) in HIV infectedpatients with CD4 < 200

Does malaria

HIV transmission?

Near 1 log HIV plasma RNA during co infection

Conflicting evidence re malaria impact on perinatal HIV transmission

Daily, J. HIV and Malaria In: UpToDate, Rose, BD (Ed), UpToDate, Waltham, MA, 2007


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clinical impact on HIV

Malaria associated with temporary HIV RNA

Episodes of malaria associated with CD4

No demonstrated difference HIV-related survival

in malaria-endemic to non endemic countries



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clinical impact on malariaIn areas of stable malaria:

HIV risk of asymptomatic malaria, clinical malaria + case fatality.

Clinical malaria frequency with lower CD4 consider HIV test if Dx clinical malaria where immunity is usual

In areas of unstable malaria:

HIV increases the risk of complicated and severe malaria and death.

Diagnosis of malaria

more complex as many other causes of fever at low CD4

Treatment of malaria

HIV infection may compromise malaria treatment; the risk with advancingHIV-related immunosuppression

Impact of HAART

risk of malaria when CD4 on HAART




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pregnancy

The effect of HIV infection on malaria in pregnant

risk of malaria parasitaemia in general, in the placenta, and at thetime of delivery

malaria parasite densities

risk of development of clinical malaria.

HIV shifts the burden of malaria complications from in their 1st +2nd pregnancy to all pregnant .

HIV impairs prophylaxis and treatment of malaria among pregnant

The effect of malaria on HIV in pregnant

Malaria contributes to HIV RNA VL, greatest among with highestparasite density, (irrespective of the degree of immunosuppression).




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pregnancy outcome

risk of adverse perinatal outcomes (esp if low CD4)

anaemia ,

low birth weight,

preterm birth,

intrauterine growth retardation (IUGR).

Areas of uncertainty

Risk of infant mortality (likely )

Susceptibility of infants to malaria

Impact on risk of maternal to child transmission of HIV




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HIV : malariaART: malaria Tx

drug interactions


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malaria prophylaxis + treatmentHIV +ve pregnant in endemic area

Bed nets

Consider IPT (if low resistance): either daily trimethoprim sufamethoxazole or at least 3 doses of sulfadoxine-pyrimethamine,

Diagnosis of malaria Where possible supplement fever based case definition with

microscopy or RDT (rapid diagnostic tests - ICT)

Treatment of malaria Same regimens as HIV ve,

Avoid sulfadoxine-pyrimethamine if on trimethoprim sufamethoxazole prophylaxis (side effects + efficacy)


World Health Organization. Guidelines for treatment of malaria 2006. http://www.who.int/malaria


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Diagnosis ?


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Measles - clinical features Incubation: 7 - 18 days

Prodrome: fever, malaise, cough, coryza, conjunctivitis.

Koplik spots on buccal mucosa, onset just before rash.

After prodrome 2 - 4 days, maculopapular rash, behind ears + face,high fever. Rash trunk + extremities, lasts for 3-7 days, +/- finedesquamation.

Non-productive cough 1-2 weeks. Complications: otitis media, pneumonia, diarrhoea, blindness,

encephalitis.

Case fatality estimated rate:

developed countries 0.1 - 1.0 per 1000 cases. developing countries 3% - 6% (20 - 30% < 12 months old) with

malnutrition + HIV

Clinical case definition (WHO)

Any person in whom a clinician suspects measles infection, orany person with fever and maculopapular rash (i.e. non-vesicular) and cough, coryza (i.e. runny nose) or conjunctivitis(i.e. red eyes)

Laboratory criteria: measles-specific IgM antibodies


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Measles

Global reported cases: > 580,000

Global estimated deaths: 345, 000

SE Asia 174 000 [126 000 - 233 000] Western Pacific 5000 [3000 - 8000]

estimated vaccine coverage: 77%

55% countries with > 90% coverage


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Impact of Maternal HIV status on infant

immunity to measles

Infants are protected from measles infection by maternal

measles Ab transferred via placenta.

Maternal HIV infection is associated with impairedplacental transfer of maternal measles Ab

The risk of acquiring measles < 9 months of age wassignificantly higher in infants born to HIV +ve women

than in infants born to HIV -ve women*.

Barinaga J, L. Skolnik P, R. Clinical presentation and diagnosis of measles. In: UpToDate, Rose, BD (Ed), UpToDate, Waltham, MA, 2007

* Scott S; Cumberland P; Shulman CE; et al. Neonatal Measles Immunity in Rural Kenya: The Influence of HIV and Placental Malaria Infections on Placental Transfer ofAntibodies and Levels of Antibody in Maternal and Cord Serum Samples. J Infect Dis 2005 Jun 1;191(11):1854-60


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HIV: measles co infection

Clinical impact

HIV +ve children may present with measles at an earlier age thanHIV ve

The clinical presentation of measles may be atypical, including theabsence of a rash.

Risk of severe, progressive measles virus infection

Measles associated syndromes include giant cell pneumonia andmeasles inclusion body encephalitis.

Diagnosis:

Serologic analysis to diagnose measles in immunocompromisedpatients may not be useful because of deficient antibody synthesis



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Measles vaccination

Ab response to measles vaccine is impaired in HIV +ve ( withCD4)

Studies in progress are evaluating the immunogenicity of measlesvaccination at younger age in HIV + children (maternal Ab, immunosuppression)

Number of measles cases can be in regions of high HIVprevalence by maintaining high immunization rates coupled withperiodic supplemental campaigns.

However vaccine failures in HIV +ve children and the potential forprolonged measles virus shedding could hinder the longtermcontrol or elimination of measles in regions of high HIV prevalence.



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Measles vaccine : WHO recommendations

Immunocompromised HIV + ve children are at risk ofdeath or severe complications following wildtypemeasles virus infection.

The balance of risk clearly favors measles immunization.

If measles virus is circulating in a community, allchildren, regardless of HIV status, should receivemeasles vaccine.

Where the chance of contracting wildtype measles virus infection is almostnil, countries with the capacity to monitor an individual's immune status mayconsider withholding measles vaccine from severely immunocompromisedHIVinfected children.

Children with moderate levels of immune suppression should continue to

receive measles vaccine.

Moss William J., Clements C. John, Halsey Neal A.. Immunization of children at risk of infection with human immunodeficiency virus. Bull World Health Organ. 2003 81(1): 61-70.


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Visceral leishmaniasis (kala azar)

Flagellated protozoa: L. donovani, L. infantum, L. chagasi

Sand fly vector

> 90 % reported from Bangladesh, India, Sudan, and Brazil Often asymptomatic / mild, but minority severe symptomatic

disease; kala-azar or black fever (fever, pancytopenia,hepatosplenomegaly)

HIV +ve severity + uncommon clinical manifestations

frequency in patients with CD4, disseminated disease occurswhen the CD4 count is less than 50 cells/L

Diagnosis: often false ve Ab (DAT) if HIV + ve High relapse rates after treatment in HIV +ve

Proposed to include visceral leishmaniasis in AIDS case definition


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Helminths and HIV

Speculated to be a potentially important interaction,

hypothesized mechanism:

Helminth infection (eg hookworm, ascaris, stronglyoides, lymphaticfilariasis, shistosomiasis, Echinococcus granulosis (hydatid))

chronic host immune activation, (dominant Th2 profile, + anergy)

risk of HIV (+TB) acquisition,

HIV VL HIV transmission + HIV progression

Implications for vaccine development, and potential for

de worming as a HIV prevention / management strategy.

Evidence is observational and often inconclusive


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Schistosomiasis and HIV

Infection with parasitic blood flukes (trematodes) schistosomes.

S. haematobiumpredominantly in Nth Africa, sub-Saharan Africa,

Middle East, India. renal and bladder (+ genital) manifestations

Infection with S. haematobiummay increase the risk of HIV infection S. haematobium egg excretion in semen is associated with the

presence of inflammatory cells in infected men

Egg-induced inflammatory lesions in the lining of the lower reproductivetract in women are associated with an increased risk of HIV acquisition

Schistosome infections may render the host more susceptible to HIV

infection by interfering with host immune responses

Concomitant schistosomiasis infection may also be a contributing factor forincreased HIV replication


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Leprosy and HIV

Ustianowski, AP, Lawn, SD, Lockwood, DN. Interactions between HIV infection and leprosy: a paradox. Lancet Infect Dis 2006; 6:350.


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HIV: leprosy co infection

Limited data available

HIV -1 seroprevalence is not clearly demonstrated to be

higher in leprosy patients Clinical spectrum of leprosy (ratio of lepromatous :

tuberculoid disease) is not altered

HIV co infection associated with rate of type 1(reversal)and type 2 (ENL) leprosy reactions

Leprosy reported as presenting as IRD in patients on

HAART Cell mediated immune responses to M lepraeappear tobe preserved in skin biopsy

Leprosy treatment outcomes appear to be unaltered

Ustianowski, AP, Lawn, SD, Lockwood, DN. Interactions between HIV infection and leprosy: a paradox. Lancet Infect Dis 2006; 6:350.


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References

World Health Organization. Guidelines for treatment of malaria 2006. http://www.who.int/malaria


World Health Organization, Malaria and HIV interactions and their implications for public health policy. Report of aTechnical Consultation Geneva, Switzerland,23-25 June 2004

Piscopo, TV, Azzopardi, CM. Leishmaniasis.[republished from Postgrad Med J. 2006 Oct;82(972):649-57; PMID:17068275]. Postgraduate Medical Journal 2007; 83:649.

Borkow, G, Bentwich, Z. Chronic immune activation associated with chronic helminthic and humanimmunodeficiency virus infections: role of hyporesponsiveness and anergy. Clin Microbiol Rev 2004; 17:1012.

Viney, ME, Brown, M, Omoding, NE, et al. Why does HIV infection not lead to disseminated strongyloidiasis?[seecomment]. Journal of Infectious Diseases 2004; 190:2175.

Brown, M, Mawa, PA, Kaleebu, P, Elliott, AM. Helminths and HIV infection: epidemiological observations onimmunological hypotheses. Parasite Immunology 2006; 28:613.

Borkow, G, Bentwich, Z. HIV and helminth co-infection: is deworming necessary? Parasite Immunology 2006;28:605.

Harms, G, Feldmeier, H. HIV infection and tropical parasitic diseases - deleterious interactions in both directions?Tropical Medicine & International Health 2002; 7:479.

Moss William J., Clements C. John, Halsey Neal A.. Immunization of children at risk of infection with human

immunodeficiency virus. Bull World Health Organ. 2003 81(1): 61-70. Barinaga J, L. Skolnik P, R. Clinical presentation and diagnosis of measles. In:UpToDate, Rose, BD (Ed),

UpToDate, Waltham, MA, 2007

Scott S; Cumberland P; Shulman CE; et al. Neonatal Measles Immunity in Rural Kenya: The Influence of HIV andPlacental Malaria Infections on Placental Transfer of Antibodies and Levels of Antibody in Maternal and CordSerum Samples. J Infect Dis 2005 Jun 1;191(11):1854-60

Ustianowski, AP, Lawn, SD, Lockwood, DN. Interactions between HIV infection and leprosy: a paradox. Lancet

Infect Dis 2006; 6:350.

HIV Malaria+Tropical Diseases

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