HIV, Pathogens, Clean Water

Charles van der Horst, MDProfessor of Medicine

University of North CarolinaVisiting Professor

Witwatersrand University

UNC: 20 years in

Lilongwe, Malawi

• 13 million people• GNI $181, the lowest in Africa• Health Care Expenditure $58

per person• Life expectancy: 39 years• 2 physicians/100,000 people

UNC Project25,000 Sq FtHigh speed satellite internetCell storage facility300 employees

2009 USAID Report Malawi

In Malawi (2004 DHS):47.8% children stunted (height for age)22% Underweight (weight for age)5.2% Wasted (weight for height)

Groome et al Vaccine 2012

39,879 children enrolled 6 wksFollowed for 5 years9,108 hospitalizations/6,328

HIV + vs HIV – Odds Ratio (95% CI)

Acute Gastrointestinestinal Infection (AGI) 5.4 (4.9, 6.0)AGI Prolonged Hospitalization 1.8 (1.4, 2.4)AGI Multiple hospitalizations 5.0 (2.9, 5.8)AGI Case fatality 4.0 (2.0, 7.8)

Proportion of infants hospitalized due to diarrhea

0

1

2

3

4

0 2 4 6 8 10 12

Age in months

Prop

ortio

n of

infa

nts

with

dia

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a (%

)

K-M curve probability of first diarrhea among HIV-uninfected infants. Rainy season= November-March

Weaning: The BAN Study

Weaning is bad!So is the rainy season!

BAN Pediatric Morbidity and Mortality AnalysisRainy season, low maternal Hgb, low infant WBC associates with increased risk of diarrhea/GF.

Infant cotrimoxizole associated with decreased diarrhea/GF

Huge Differential of HIV Associated Diarrhea

• Few comprehensive studies in subSaharan Africa• Beware saprophyte/colonizer vs pathogen• Protozoa (Cryptosporidium, Microsporidia,

Cyclopspora, Isospora belli, Giardia, Entamoeba, Blastocystis, Dientamoeba

• Viruses (Rotavirus-Vaccine preventable!, CMV)• Bacteria (E Coli, Vibrio Cholera-vaccine, Salmonella,

Shigella, Campylobacter, Mycobacterium avium, C difficile)

Increased disease burden with lower CD4 counts

Cryptosporidia• Water-borne• Highly infectious• Refractory diarrhea• Multiple GI tract surfaces• Destroys enterocyte• Malabsorption• Found in water in hospitals

(Martins, C. A. P., 1995) and home (Aragon, T. J. 2003)

• Dx with single stool Acid fast stain• No studies on prevention and few

treatments work well (Abubakar, I. et al., 2007) (? Nitazoxanide (CIII).

Microsporidiosis

• 3 Stools stained with chromotrope or chemofluorescent stain (Calcifluor white)

• A few strains respond to albendazole

Cyclospora cayetanensis• Coccidian parasite related to

Eimeria sp• Ingestion of contaminated fruits

and vegetables• Infects enterocytes in proximal

small intestine– Chronic, non-bloody diarrhea

and weight loss• May be confused with

cryptosporidia, though spores are larger 8-10 µm)

• Dx with modified acid fast stain• Responds to sulfonamides

(TMP-SMX 160-800 for 7-10 days)

Isospora belli· Found in travelers and

residents from endemic areas

· Watery diarrhea · Eosinophilia· Malabsorption· Dx with modified acid fast · Treatment/ prophylaxis with

sulfonamides

Giardiasis• Diagnosis

– Stool O&Px3, 85% positive in acute cases, lower in chronic cases

– Fecal stool antigen• Treatment

– Metronidazole: 250 mg tid for 5-7 days

– Paromomycin in pregnancy?

– Treatment of asymptomatic carriers not recommended

MAC• Evidence that MAC spread through hospital water to

patients (Hillebrand-Haverkort, M. E. et al., 1999). – Increased risk of “induced disseminated

mycobacteremia rather than bacteria restricted to the lungs,” in PLHIV with MAC

– MAC is ubiquitous in soil and water and highly resistant to chlorine (Biet, F. et al., 2005)

P&G Packet Study: IntroductionXue J, Mhango Z, Hoffman IF, Mofolo I, Kamanga E, Campbell J, Allgood G,

Cohen MS, Martinson FE, Miller WC, Hosseinipour MC.Trop Med Int Health. 2010 Oct;15(10):1156-62

• Offer clean water to patients infected with HIV to reduce diarrheal illnesses

• UNC idea: the triple whammy– Provide packets to mothers with HIV to reduce

diarrheal illnesses– Treatment of the mother might reduce diarrheal

illnesses in the infants– The program, which requires multiple visits, will

allow better care for the infant

P& G Packet Study: Methods• 2 District health centers in Lilongwe where PMTCT

programs were ongoing (area 18 and area 25) • Monthly visits for HIV infected mother and exposed

or infected infant from 6 months to 18 months post-partum

• Prospective, observational design over 3 month F/U• Monthly self report about product use and diarrhea• Retention, diarrhea compared to historic values

Monthly service provided• Hygiene, nutrition, breastfeeding and

family planning counseling • 4kg of vitamin fortified porridge (VitaMeal, from Feed the Children)• P&G Packets with filter cloth• Water storage container with lid and spout

(once)• Bar soap • ART and primary care clinic referrals

Baseline Results (October 2008-March 2009)

• 474 mother infant pairs enrolled• Median age of infants: 11.7 months (2.4-24

months)• 34 (7.2%) infants were HIV infected• 16 (47.1%) infants on ART (universal for <12

mo)• 195 (41.1%) mothers on ART (CD4 <350)• 386 (81.4%) community tap water

Retention and Follow-up (initial, and 3 monthly visits) n=474

• 301(63.5%) completed 3 or more visits • 357 (75.3%) remained in F/U at 3 months • At the 3 month visit: • Only 48 (13.5%) of the infants had an unknown

HIV status• 355 women (99.4%) reported using the water and

hygiene products at home• 332 infants (93.0%) were on replacement feeding

Diarrhea Reported in last month of F/Un=357

# Diarrhea % Diarrhea 95% CI

Mothers 3 0.8% 0.2-2.4%

Infants 17 4.8% 2.8-7.5%

Reported Infant Diarrhea at 3 month F/UCompared to Malawi DHS 2004

Age (mo) Post natal program % Diarrhea /4 wks N=357

Malawi DHSDiarrhea/2 weeksN= 9777

<6 0 (n=1) 9.2 (n=1109)

6-11 7.6 (n=119) 41.2 (n=1188)

12-23 3.5 (n=231) 38.9 (n=2194)

>24 0 (n=6) 8.3-21.5 (n=5286)

Limitations • Diarrhea/ product use data is all self report • Used historic data as our comparison group• No data from those infants and mothers LTFU

3.8 million people130 antenatal clinics153,000 pregnancies

Safeguard the Family: A New Challenge

Introduce Comprehensive Care• Insecticide treated mosquito nets• Vaccinate all babies AND siblings• Routine HIV testing to entire family• Depoprovera and IUDs• Active TB screening • Clean water (P&G Packets)• Linkage to HIV Care• Electronic Medical Record

FPHIV TBMCH

WASH

Funding Provided by • National Institutes of Health

– ACTG, CFAR, ICORTA-TB/AIDS, Fogarty Global Health Fellows

• Centers for Disease Control and Prevention (The BAN Study)

• USAID (Safeguard the Family)