Transcript document

Welcome to I-TECH HIV/AIDS
Clinical Seminar Series
HIV and Tropical Diseases
Judd Walson, MD, MPH
April 22, 2010
Case #1
• 23 year old female presents to HIV Care Clinic
where she receives care complaining of fever
for 1 day.
• Family lives in an area that is holoendemic for
malaria.
• She is anemic (Hb of 6.5), tachypneic, mildly
confused and has fever to 40.1 C.
Malaria and HIV
Classification of endemicity
Type
Spleen Rates
Parasite Rates
Description
Hypoendemicity
<= 10% of children
aged 2-9 years
<= 10% of
children aged 29 years but may
be higher for
part of the
Areas where there is a little
transmission and the effects,
during the average year, upon
the general population are
unimportant
Mesoendemicity
11-50% of children
aged 2-9 years
11-50% of
wide geographical variations
children aged 2- in transmission risk exist
9 years
Hyperendemicity
Constantly > 50% in
children aged 2-9
years; also high in
adults (>25%)
Constantly >
50% among
children aged 29
Areas where transmission is
intense but seasonal;
immunity is insufficient in all
age groups
Holoendemicity
Constantly > 75% in
children aged 2-9
years, but low in adults
Constantly >
75% among
infants aged 011 months
Intense transmission resulting
in a considerable degree of
immunity outside early
childhood
http://www.malaria.am/eng/epidemiology.php
Immunology
•CD4 cells play a role in the
development and
maintenance of immunity
against malaria
•Shift towards a Th2 type
response to clear chronic
malaria infection
•Induction of regulatory T
cells with production of
suppressive cytokines
(hyporesponsiveness)
•Poor B cell response leads to
reduced clearance of
parasites
Effects of HIV-1 on Malaria Incidence
and Severity
Laufer MK et al. Impact of HIV-associated immunosuppression on malaria infection and disease in Malawi. The Journal of Infectious
Diseases 2006; 193:872–8
Laufer MK et al. Impact of HIV-associated immunosuppression
on malaria infection and disease in Malawi. The Journal of
Infectious Diseases 2006; 193:872–8
French N et al. Increasing rates of malarial fever with deteriorating
immune status in HIV-1-infected Ugandan adults. AIDS 2001 vol. 15
(7) pp. 899-906.
Case #1
• 23 year old female presents to HIV Care Clinic
where she receives care complaining of fever
for 1 day.
• Family lives in an area that is holoendemic for
malaria.
• She is anemic (Hb of 6.5), tachypneic, mildly
confused and has fever to 40.1 C.
Case #1
• Any other info needed?
• What testing needed?
• What treatment needed?
The diagnosis of Malaria
• Malaria is often over diagnosed!
• Most clinics and hospitals in Africa do NOT do
any testing but make a clinical diagnosis of
malaria
The diagnosis of Malaria
• The sensitivity and specificity of malaria thin
and thick smears are 50% and 96%
respectively.
• The proportion of patients with positive
smears DECREASES with age.
• In endemic areas, a positive smear may
confirm malaria…but is that why the patient is
sick??
Malaria Journal 2006, 5:4, BMJ 2004; 329; 1212
BMJ 2004;329:121
Tanzanian Study
• 4474 people admitted to hospital met criteria
(clinical) for severe malaria.
• 2062 (46.1%) had positive slides
• 2375 were slide negative
– 66.1% did NOT receive antibiotics
– Case fatality rates were significantly different
• 12.1% in the slide negative patients (16.5% in age>15)
• 6.9% in the slide positive patients (10.7% in age>15)
BMJ 2004;329;1212-
Malaria and Bacteremia
JID 2007;195; 985-904.
Case #1
• Attending clinic since diagnosis 11 months
ago.
• CD4 count 437 cells/mm3 about 9 weeks ago.
• ART naïve.
• On co-trimoxazole for past 7 months.
• Thin Smear POSITIVE for P. falciparum with a
parasite density of 600 parasites per microL
(7.5%).
Treatment
• 23 year old female with documented
parasitemia, CD4 count of 437 cells/mm3, on
co-trimoxazole.
– What are the treatment options?
– Doe the fact that she is on co-trimoxazole and
NOT on ART matter?
Co-trimoxazole?
• Why do we use co-trimoxazole in Africa?
• What are the implications for treatment of
malaria in a patient on co-trimoxazole?
• What other interventions can we add to
prevent malaria? Are any of these beneficial if
the patient is compliant with co-trimoxazole?
co-trimoxazole
• co-trimoxazole reduces MORTALITY in HIV
infected individuals in Africa!!! (46% reduction in
mortality in Uganda).
• co-trimoxazole decreases rates of malaria,
diarrhea and hospitalizations in those on
prophylaxis.
• co-trimoxazole taken for prophylaxis reduces
mortality in family members (63% percent less
mortality in children less than 10!) and reduces
malaria, diarrhea and hospitalizations in family
members as well!
Lancet 2004; 364 (9443) pp. 1428-34, AIDS; 2005; 19 (10) pp. 1035-42
Resistance
• There is demonstrated in-vitro cross-resistance
between SP (fansidar) and co-trimoxazole.
• Most countries do NOT use SP as first line malaria
treatment (except IPT for pregnant women!)
• In a randomized trial of co-trimoxazole to prevent
malaria, there was no demonstrated increase in
resistant parasites over 12 weeks and cotrimoxazole was 99.5% effective in preventing
clinical malaria.
JID 2005;192;1823.
Additional Interventions
• Bednets – In Uganda, insecticide Treated Nets
(ITN’s) resulted in a 40% reduction in the
incidence of symptomatic malaria, OVER AND
ABOVE the benefit seen with prophylactic cotrimoxizole.
• ITN’s are simple, effective, and, in contrast to
TMP/SMZ, do not pose risk to the individuals
of drug toxicity or development of resistant
microbial flora.
Lancet. 2006;367:1256-61.
Treatment and ART
• Efavirenz is metabolized by CYP 3A4 and alters
artesunate and amodiaquine levels (may result in
increased liver toxicity) NOT DEMONSTRATED.
• Ritonovir inhibits P450 and may increase
mefloquine and artemisinin levels. (One study
showed increased neutropenia in children on ART
receiving artesunate plus amodiaquine.
• Most protease inhibitors have direct anti-malarial
activities (? Effective prophylaxis?)
Clin. Infect. Dis. 46, 985–991, Trends in Parasitology. 24 (6) pp. 264-71
Effects of Malaria on HIV-1
Hoffman IF et al. The effect of Plasmodium
falciparum malaria on HIV-1 RNA blood plasma
concentration. AIDS 1999 vol. 13 pp. 487-494
J . Kublin , P . Patnaik , C . Jere , W . Miller , I . Hoffman , N . Chimbiya , R . Pendame , T . Taylor , M . Molyneux. Effect of Plasmodium
falciparum malaria on concentration of HIV-1-RNA in the blood of adults in rural Malawi: a prospective cohort study. The Lancet
, Volume 365 , Issue 9455 , Pages 233 – 240.
Effect of modest VL reduction
Gupta et al. JID 2007; 195 (Feb 15).
Abu-Raddad LJ et al. Dual infection with HIV and malaria fuels the spread of both
diseases in sub-Saharan Africa. Science 2006 vol. 314 (5805) pp. 1603-6.
Summary Malaria and HIV
• HIV infected individuals are at risk for more
frequent and more severe malaria. Both are CD4
count dependent.
• Malaria increases plasma viral load. This may
have important implications for both HIV disease
progression and transmission.
• Co-trimoxazole works for patients and their
families and benefits ALL HIV infected individuals
in resource poor settings REGARDLESS OF CD4
COUNT.
CASE # 2
• 38 year old man presents to clinic with
complaints of weight loss. Slowly losing
weight over past year (from about 60kg to
54kg).
• No other complaints (no fever, cough, chills,
etc.)
• Says he has noticed large 6-7cm worms in his
stool.
CASE # 2
• Given weight loss, HIV testing advised and
performed and patient is HIV positive.
• Stool test done and is positive for eggs of
Ascaris lumbricoides and hookworm species.
WHAT SHOULD BE DONE (IF ANYTHING?).
Distribution of helminths and HIV-1 in
Africa
Clinical Microbiology Reviews, October 2004, p. 1012-1030, Vol. 17, No. 4
Epidemiology
 Over 2 billion people are estimated to be infected with
at least one species of helminths.
 In fact, about 25% of the worlds population is infested
with one or more soil transmitted helminth.
 Of the approximately 25 million people infected with
HIV-1 in Africa, as many as 50-90% may also be infected
with a soil transmitted helminth.
1.
Helminth egg burden correlated with
HIV-1 viral load
J Acquir Immune Defic Syndr, Volume 31(1).September 1, 2002.56-62
Walson JL, John-Stewart G. Treatment of helminth co-infection in HIV-1 infected individuals in resource-limited settings. Cochrane Database of
Systematic Reviews 2008, Issue 1. Art. No.: CD006419. DOI: 10.1002/14651858.CD006419.pub2.
AIDS 2008; 22:1–9.
Effects on CD4 and Viral Load
AIDS 2008; 22:1–9.
Case #3
• An HIV infected mother brings her 1 year old
son in to clinic because his sibling (age 3) has
had “measles” (diagnosed at local facility).
• The child is HIV positive by antibody testing.
• Currently the child is well, playing and does
not appear ill.
– What can/should be done to protect the child?
– What other interventions/testing could be done
for the child?
Measles and HIV
• Measles is exacerbated by HIV infection.
• HIV infected individuals shed the virus longer.
• Vaccination is less effective in individuals with
HIV.
• Measles vaccine is a “live” virus vaccine so
there may be risks with it’s use.
HIV and Measles - Mortality
Measles occurs at younger ages (more likely to occur at
age <9 months)
AND
is associated with increased mortality even after
controlling for age, sex, and measles vaccination
status.
CID 2008; 46:523-7.
PREVENTION
• In areas where there is a risk of measles
transmission – ALL children (including those
with HIV – regardless of degree of
immunosuppression) should be vaccinated??
• Consider early vaccination in HIV infected
children at 6-9 months
• Where available, monthly IgG can be given to
exposed children who have poor vaccine
response.
CID 2007. 45 (9) pp. 1214-20
Treatment
• Supportive care
• Vitamin A – shown to reduce mortality and
lead to more rapid resolution of pneumonia
and diarrhea. Most data in children under 2.
• ?Ribavirin where available for severe cases.
No RCT data.
N Engl J Med 1990 Jul 19;323(3):160, JAMA 1989 May 5;261(17):2512-6.
Thank you!
Next session: May 6, 2010
HIV Dermatology – Most Interesting Case Contest
Dr Roy Colven