Infectious Diseases in Resource-Limited Settings

Report
Ramona Bhatia, MD

Tuberculosis (TB)
◦ Epidemiology
◦ Diagnostics and treatment
◦ Prevention and student health issues

Malaria

Human immunodeficiency virus (HIV)
◦ Epidemiology
◦ Diagnostics and treatment
◦ Prophylaxis for travelling students
◦ Epidemiology
◦ Diagnosis and treatment
◦ Needlesticks and post-exposure prophylaxis (PEP)

Undergraduate and medical training at
Northwestern
◦ Clinical experience in India

Residency at Baylor College of Medicine,
Houston, TX
◦ County and VA hospital settings

Fellowship in Infectious Diseases at
Northwestern
◦ HIV outcomes
◦ HIV and global health

Research Associate and Clinical Instructor

8.7 million new cases
◦
◦
◦
◦

13% in HIV-infected (HIV+) patients
India/China->40%
Africa (South Africa>Nigeria)-> 24%
Americas-> 3%
1.4 million TB-related deaths
◦ 990,000 in HIV-uninfected (HIV-)
◦ 430,000 in HIV+
◦ One of the top three causes of death for adult
females in resource-limited settings (RLS)
WHO Global Tuberculous Control , 2012
WHO Global Tuberculous Control , 2012

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After inhalation, TB may symptomatically infect
the lower lobes of the lung (primary TB
infection)
Or, the bacteria are contained in upper lobes
by macrophages and cell-mediated immune
responses (latent TB infection, LTBI)
◦ Can progress to symptomatic disease later
(reactivation or “active” TB)

Other patients may completely clear the
organism

Lifetime risk of reactivating TB is 10% in those
with LTBI
◦ 5% in the first two years
◦ 5% thereafter

In untreated HIV+ patients, the risk is 7-10%
per year
◦ HIV is the strongest predictor of progression

Other immune compromising conditions
associated with reactivation:
◦ Diabetes
◦ TNF-α inhibitor use
◦ Steroid use
www.cdc.gov

WHO Symptoms Screen
◦ Absence of all of: cough, weight loss, fever, night sweats
◦ Commonly used in HIV+ patients

Tuberculin skin test (TST)
◦ Look for induration (10 mm in med students, 5 mm in
HIV+) after 48-72 hours
◦ A positive test indicates prior exposure
◦ Not always positive in active TB
◦ Recommended in RLS

Interferon-γ Release Assay (IGRA)
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◦
◦
◦
Looks for in-vitro reaction
A positive test indicates prior exposure
Not always positive in active TB
Not recommended in RLS

Acid-fast staining of
sputum
◦ Analyze 3 early morning
samples
◦ Most common method in RLS

Mycobacterium
tuberculosis culture
◦ May not be widely available
in RLS

Molecular techniques (i.e.,
PCR)
◦ Uncommon in RLS
◦ Point of care tests are
available (GeneXpert)

Chest X-Rays
◦ Uncommon in RLS
Univ. S. Carolina School of Medicine


Preferred regimen has been 9 months of daily
isoniazid (INH)
Other regimens
◦ 4 months of daily rifampin (RIF)
◦ 3 months of weekly, directly-observed INH plus
rifapentine

First-line treatment-> RIPE
◦ Early intensive phase: 2 months of RIF, INH,
pyrazinamide (PZA), and ethambutol (ETH)
◦ Continuation phase: 4 months of RIF and INH

Monitor monthly for liver toxicity
◦ Usually from INH>RIF>PZA
◦ In RLS, use the physical examination (scleral icterus,
jaundice, and hepatomegaly)
◦ Liver function testing is not widely used

Other side effects: rash, GI disturbance,
ocular toxicity, and neuropathy
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MDR-TB: INH and RIF resistant
XDR-TB: MDR-TB isolates that are also
resistant to an injectable (i.e., aminoglycoside)
and a quinolone
They have been found in all regions
◦ MDR-TB: 3.7% of new TB
◦ High prevalence in Eastern Europe

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Longer treatment (20 months) with more side
effects
Higher mortality
WHO Global Tuberculous Control , 2012
WHO Global Tuberculous Control , 2012


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In one study of American students travelling
to Kenya, risk of converting the TST was 4.1%
There was no association with duration of
stay or participation in direct medical care
Only 27% of students reported “ideal” TB
prevention measures and monitoring

Vaccine?
◦ No. The BCG vaccine is used abroad to prevent
childhood TB. It is not available in the U.S.

Medical prophylaxis?
◦ No medications are available for TB prophylaxis

Best approach involves limiting exposure and
monitoring for disease

Current international guidelines recommend
triage and isolation of patients suspected to
have active TB, but space and resource
limitations may preclude this
◦ Especially critical to isolate from HIV+ patients

Negative pressure rooms are uncommon
◦ Guidelines recommend natural (i.e., opening
windows) or mechanical (i.e., fans arranged to blow
air out of room) ventilation
Personal respiratory protection is the main
option for limiting exposure

◦ Obtain 1box of N95 masks online
◦ Reuse masks
◦ Use when seeing a patient with a positive symptoms
screen or who is suspected to have active TB
◦ Share with the host medical team
 They may not have N95 masks or may only be using
them for invasive procedures (i.e., intubations)

Students should never be seeing patients with
known or suspected MDR-/XDR-TB

All student travelers should undergo testing
for LTBI with TST or IGRA prior to leaving
◦ Addressed at student health appointment


Repeat LTBI testing 8-10 weeks after
returning
Self-monitor for:
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Fever (can occur 2-8 weeks after exposure)
Night sweats
Weight loss
Cough
Others: lymphadenopathy, hemoptysis, pleurisy, etc.

216 million cases in 2010
◦ Large burden of disease (81%) and disease-related
mortality (91%) in sub-Saharan Africa
◦ One child dies every minute from malaria in Africa

In the U.S., 8,117 travel-related cases
reported over last decade
◦ 66% acquired from sub-Saharan Africa
◦ 14% acquired from Asia
◦ 43 fatalities, mostly from Plasmodium falciparum
infection acquired in sub-Saharan Africa


This is a general map
that does not reflect the
within-country variation
of malaria endemnicity
Transmission depends
on survival patterns of
the Anopheles vector
CDC Yellow Book, 2012
CDC Yellow Book, 2012

Blood-borne transmission after bite of
Anopheles mosquito
◦ P. falciparum, ovale, vivax, and malariae
◦ Transmission can occur after needlesticks

In high-burden countries, transmission is
stable and most develop immunity
◦ Pregnant women, children, HIV+ patients, and
visitors continue to be at risk

In low-burden countries, transmission is
sporadic and immunity may not develop

In RLS, patients with fever are commonly
empirically treated for malaria
◦ This strategy is associated with overtreatment and
development of drug resistance
◦ Other symptoms: conjunctival or palmar pallor
◦ End organ dysfunction (i.e., low urine output,
altered mental status) defines “severe malaria”

Ideally, obtain blood smears or rapid tests
prior to starting therapy
◦ If a patient is unstable, empiric therapy is warranted

Artemisinin-based combination therapy (ACT)
is recommended for uncomplicated
P.falciparum malaria
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Artemether plus lumefantrine (Coartem)
Artesunate plus amodiaquine
Artesunate plus mefloquine
Artesunate plus sulfadoxine-pyrimethamine
Dihydroartemisinin plus piperaquine
Choice of preferred ACT is country-specific
Severe malaria
◦ “ABCs” for the critically ill
◦ Hospitalize and start IV or IM artesunate

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The geographic risk of malaria will be
determined at the pre-departure student
health appointment
Prevention has four elements:
◦
◦
◦
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A-awareness of the disease process
B-avoid being bitten with effective vector control
C-chemoprophylaxis adherence
D-diagnosis should infection occur
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http://www.malariaconsortium.org/
Insecticide-treated
nets (ITNs)
Long sleeves and
pants
Insect repellant
o DEET (10-50%)

Atovaquone-proguanil (Malarone)
◦ Daily dosing
◦ Start 1-2 days prior to leaving; continue for 1 week
after returning
◦ Overall well tolerated
◦ Contraindicated in severe renal failure

Mefloquine
◦ Serious CNS side effects can occur

Chloroquine, hydroxychloroquine
◦ Not used due to high rates of resistance

Doxycycline
◦ Sun sensitivity

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
Watch for fever
Incubation is 1 week, so fever immediately
after exposure to an endemic area is unlikely
malaria
If symptoms occur, seek medical care
◦ List of reputable clinics in your area will be
provided to you
◦ DO NOT use medications from marketplaces (high
rates of ineffective, expired, and unregulated meds)

34 million people living with HIV/AIDS (PLWHA)
◦ 2.2 million in North America/Europe
◦ 22.9 million in sub-Saharan Africa (5.6 million in
South Africa)

2.7 million new infections
◦ 88,000 in North America/Europe
◦ 1.9 million in sub-Saharan Africa

1.8 million deaths due to HIV/AIDS
◦ 30, 000 in North America/Europe
◦ 1.2 million in sub-Saharan Africa
CDC Yellow Book, 2012


HIV infects CD4+ T-lymphocytes (CD4 cells)
Transmitted through sexual fluids,
breastmilk, or blood
◦ Possible transmission through oral sex but rare
◦ No transmission from kissing or close contact
◦ No transmission from fomites
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In acute infection, flu-like syndrome with
rash, lymphadenopathy, and/or meningitis
Or can be completely asymptomatic
In chronically infection, symptoms are often
from opportunistic infections (OI)

TB is the most common OI in HIV+ patients
◦ Occurs at any CD4 count
◦ One-third of HIV+ patients also have LTBI

TB is the most common cause of death in
HIV/AIDS patients in Africa and a leading
cause globally
◦ 350,000 deaths yearly worldwide

All patients with TB should be tested for HIV;
all patients with HIV should be screened for
TB

All HIV+ patients should undergo symptom
screening for TB and (if negative) receive INH
preventative therapy (IPT)
◦ In RLS, PPD, IGRA, and CXR not routinely used

Presentation of active TB depends on CD4
count. In general:
◦ Immunocompetent (CD4>300/µl): pulmonary TB,
cavities, granulomas
◦ Immunosuppressed (CD4<300/µl): extra-pulmonary
TB (virtually anywhere including blood, lymph nodes,
GI tract, CNS), atypical/normal CXR, +/-granulomas
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Occurs at CD4 count
<50/µl
Subacute mental status
changes, headache,
fever common
CSF may be normal
In RLS, may treat with
fluconazole
 Amphotericin may
not be available
India Ink, www.stanford.edu
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Occurs at CD4 count<100/µl
Focal neurologic signs, fever,
headache common
Ring-enhancing lesions
Treat with pyrimethamine
plus sulfadiazine plus
leucovorin (folinic acid)
◦ Some RLS may utilize
sulfadoxine instead of
sulfadiazine
www.radiopaedia.com

In U.S., common screening test is ELISA
◦ High sensitivity


In RLS, rapid serologic HIV testing more
common for screening
Confirmatory test for both is Western Blot
◦ High specificity

In suspected cases of acute HIV, obtain HIV
viral load
◦ The other tests may be negative
◦ HIV viral load may not be available in all RLS
U.S. (AIDSinfo)
RLS (WHO)
Indication?
All HIV+ patients
CD4<350/µl or stage 3
or 4 (i.e., presence of
OI)
What to initiate?
Several regimens are
first-line; more being
added
Only zidovudine,
lamivudine,
emtricitibine, tenofovir,
efavirenz, nevirapine
first-line
How to monitor?
CD4 count, viral load,
clinical assessment
CD4 count and clinical
assessment (viral load
only if available)
Pregnant women?
All women (lifelong
treatment)
All women (lifelong or
pregnancy-only
treatment)

Know what defines a high-risk exposure:
An exposure that might place HCP at risk for HBV, HCV, or HIV
infection is defined as a percutaneous injury (e.g., a needlestick or cut
with a sharp object) or contact of mucous membrane or nonintact skin
(e.g.,exposed skin that is chapped, abraded, or afflicted with
dermatitis) with blood, tissue, or other body fluids

Potentially infectious:
blood, CSF, synovial fluid, pleural
fluid, pericardial fluid, amniotic fluid, semen, vaginal secretions

Not infectious:
feces, nasal secretions, saliva, sputum,
sweat, tears, urine, and vomit, as long as these are not visibly
contaminated with blood

Avoidable high-risk behaviors:
◦ Tattoos, piercings, acupuncture
◦ Sexual activity
◦ Drug use
Use standard precautions if using
sharps
 Needlestick risks of infection:

◦ HIV: 0.3% (approx. 1000 cases/year)
◦ Hepatitis C: 3.0%
◦ Hepatitis B: 30%


Immediately flush area with soap and water
Obtain source source rapid HIV test and hepatitis B
and C serologies
◦ The hepatitis testing may not be readily available

Exposed student should know his/her baseline
serologies
◦ All med students should have received hepatitis B vaccine
with follow-up HepBSAb pre-departure
◦ Pre-departure HIV testing encouraged
◦ HIV, hepatitis B, and hepatitis C serologic testing should
be performed after exposure

Report exposure to attending/supervisor and
Northwestern contact (Dan Young, Dr. Thomas, Dr.
Sanguino)-but should not delay testing or PEP!

Hepatitis B
◦ If student HepBSAb positive (i.e., >100IU/L), no
action needed
◦ If student HepBSab negative or unknown,
administer hepatitis B vaccine and HBIG
(immunoglobulin) within 24 hours and repeat
serologies at 1 and 3 months

Hepatitis C
◦ In addition to baseline student testing, obtain
repeat serology at 1, 3, and 6 months
◦ OR obtain PCR at 4-6 weeks
◦ No recommended PEP

Initiate PEP ASAP if source is HIV+, HIV
unknown, or may be in the window period
with false-negative rapid testing
◦ MUST BE within 72 hours but do not wait this long!

Many host hospitals have PEP on hand
◦ ASK about PEP policies on the first day of work!

Monitor for side effects: diarrhea common
◦ Fevers, rashes, intolerable GI side effects need to be
further evaluated
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PEP duration 28 days… Adherence is crucial!
Follow-up testing at 1, 3, and 6 months

After needlestick, student should selfmonitor for symptoms
◦ Flu-like illness
◦ Lymphadenopathy
◦ Abdominal pain or jaundice
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Student can continue to work in the hospital
Student should refrain from donating blood
or unprotected sexual activity for 6 months
On returning home, student will see an ID
physician for repeat serologies as needed and
PEP monitoring
You are rotating on the general medicine
ward in a hospital in Cape Town, South Africa.
You are asked to help out a friend who is doing
a lumbar puncture on a cachectic patient with
altered mental status of unknown etiology.
Your friend is startled, and the needle
punctures through his glove and into his skin.
You are not wearing goggles, and the fluid gets
into your eyes.
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Has there been a high-risk exposure?
What is the very first thing that should be
done?
What should be done next?
How could this have been prevented?
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There is a large burden of TB, malaria, and
HIV in RLS
The management of these infections may be
different in RLS
Students should engage in prevention
strategies to protect themselves from these
infections
Host attendings/supervisors and
Northwestern Global Health contacts are
available for any concerns during travel

Infectious Diseases Clinic
◦ Drs. Murphy, Galvin, Achenbach, Bhatia
◦ 312-695-8358

Travel Clinic
◦ Dr. Lee
◦ 312 926-3155
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WHO recommended IC practices:
1.
2.
3.
4.
Triage pt with TB –depends on region
Isolate TB pts ESP from HIV pts
Cough etiquitte for TB pts (unknown if a mask on them helps)
Natural and mechanical ventilation (fans)
In particular, health workers should use particulate respirators:
• during high-risk aerosol-generating procedures associated with
high risk of TB transmission (e.g. bronchoscopy,
intubation, sputum induction procedures, aspiration of respiratory
secretions, and autopsy or lung surgery with highspeed
devices)
• when providing care to infectious MDR-TB and XDR-TB patients or
people suspected of having infectious MDR-TB
and XDR-TB.
http://whqlibdoc.who.int/publications/2009/9789241598323_eng.
pdf

People working internationally who will be engaging in high-risk occupational health care activities, such as drawing blood or the other use of sharps during patient care, should
consistently follow standard precautions to reduce the risk of occupational exposure to HIV and other bloodborne pathogens. Standard precautions involve the use of protective
barriers such as gloves, gowns, aprons, masks, or protective eyewear. Additional information about occupational health and safety standards for bloodborne pathogens can be
found at http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=STANDARDS&p_id=10051

In addition, clinicians working internationally should:

Always be mindful of the hazards posed by sharps injuries.

Maintain strict safety standards while working in environments that may have less stringent standards.

Use devices with safety features and improved work practices (www.cdc.gov/niosh/docs/2000-108/).

Consider bringing their own protective equipment if they are unsure of its availability at their destination.

Consider bringing postexposure prophylaxis (PEP) for HIV in the event that they are injured with a potentially contaminated sharp.

POSTEXPOSURE MANAGEMENT

Health care workers who may have been occupationally exposed to HIV should immediately perform the following steps:

Wash the exposed area with soap and water thoroughly. If mucous membrane exposure has occurred, flush the area with copious amounts of water or saline.

If possible, assess the HIV status of the source. Rapid HIV testing is preferred. If the source’s rapid HIV antibody test result is positive, assume that it is a true positive.

Seek qualified medical evaluation as soon as possible to guide decisions on postexposure treatment and testing.

Contact the National Clinicians’ Postexposure Prophylaxis Hotline (PEPline) at 1-888-448-4911 (24 hours a day, 7 days per week) for assistance in assessing risk and advice on
managing occupational exposures to HIV and other bloodborne pathogens (www.nccc.ucsf.edu/about_nccc/pepline). If the toll-free number is not accessible when calling from
another country, the main administrative line for the National HIV/AIDS Clinicians’ Consultation Center is 415-206-8700.

Consider beginning PEP for HIV (see below).

Postexposure Prophylaxis

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A number of medication combinations are available for PEP. Since these regimens may change based on new research, refer to MMWR’s Updated US Public Health Service
Guidelines for the Management of Occupational Exposures to HIV and Recommendations for Postexposure Prophylaxis
(http://aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?MenuItem=Guidelines&Search=Off&GuidelineID=10&ClassID=3) and the PEPline for more information about PEP
recommendations. Specific regimens should be determined by clinicians familiar with the medications and the health care worker’s medical history.
If the exposed person chooses to initiate PEP, he or she must do so within hours of the exposure. PEP can be stopped if new information changes the assessment; however,
waiting to start PEP until all information is gathered can decrease its efficacy. If indicated, arrange for procurement or shipment of additional PEP from a credible source to
complete the recommended 4-week course of treatment.

Consider other potential infectious disease exposures from the source material, including hepatitis B virus or hepatitis C virus (HCV), and manage as appropriate.

Postexposure Testing
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People with occupational exposure to HIV should receive HIV antibody testing by enzyme immunoassay as soon as possible after exposure as a baseline, with follow-up testing
at 6 weeks, 3 months, and 6 months. Extended HIV follow-up testing for up to 12 months is recommended for those who become infected with HCV after exposure to a source
coinfected with HIV and HCV. Postexposure counseling and medical evaluation should be provided, whether or not the exposed person receives PEP
(http://aidsinfo.nih.gov/contentfiles/Health CareOccupExpoGL_PDA.pdf ).
Exposed health care workers should be advised to use precautions (avoid blood or tissue donations, breastfeeding, or pregnancy) to prevent secondary transmission, especially
during the first 6–12 weeks after exposure. For exposures for which PEP is indicated, exposed people should be counseled regarding possible drug toxicities and interactions,
the need for monitoring, and the importance of careful adherence to PEP regimens.
Cdc yellow book 2012

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