Malaria_NEHC_IDC_20020

MALARIAPrevention and Control : 

MALARIAPrevention and Control Navy Environmental Health Center Portsmouth, VA (757) 953-0710

Course Objectives : 

Course Objectives Basic understanding of malaria Epidemiology Symptoms Diagnosis Treatment Prevention

What Is It? : 

What Is It? A mosquito-borne infectious disease Protozoan parasites of the genus Plasmodium Transmitted only by Anopheles Mosquitoes Disease can be: Acute Chronic Four species: P falciparum P vivax P ovale P malariae

Why The Concern? : 

Why The Concern? Most prevalent disease in the world 2.1 billion live in MALARIOUS areas 100-300 million new cases annually 1-3 million deaths annually Potentially lethal disease January-March 2000: Two U.S. citizens died of malaria after taking inappropriate chemoprophylaxis Serious threat to military personnel

Slide 6: 

AFRICA, ASIA, LATIN AMERICA, CARIBBEAN Tropics, subtropics, fringes of temperate forests Map Source: www.wehi.edu.au/research/infimm/malaria1.html

History : 

History WWI Naval Forces 4,746 new hospital admissions 68,373 lost man-days 7 deaths WWII Naval Forces 111,675 new hospital admissions 3,310,800 lost man-days 90 deaths 5,332 (AVG) daily sick list in pacific

History : 

History Vietnam War Naval Forces 21,695 new admissions 187,478 lost man-days 46 deaths

Transmission : 

Transmission Man is the only important reservoir Vector is female Anopheles mosquito Temperature: below 86º F, above 68º F Rainfall: thrive in tropical areas Altitude: rarely exist above 2000 meters Terrain: coastal areas and lowlands with lots of freshwater breeding sites

Transmission : 

Transmission Mosquito vector: ANOPHELES Transmission also possible through: Blood transfusion Contaminated needle Organ transplant Congenital

Susceptibility : 

Susceptibility Universal susceptibility No absolute immunity Partial immunity in areas of high endemicity

Pathogenesis : 

Pathogenesis RBC destruction Immune complexes and mediators Capillary permeability Tissue hypoxia

Plasmodium Species : 

Plasmodium Species P. falciparum Most severe and prevalent 40-60% of cases Widespread CHLOROQUINE resistance Infects RBCs of all ages—Heavy parasitemia

Plasmodium Species : 

Plasmodium Species P. vivax 30-40% of cases Liver phase INFECTS YOUNG RBCs: LESS SEVERE THAN FALCIPARUM P. ovale Liver phase INFECTS YOUNG RBCs P. malariae Can persist SUBCLINICALLY for extended periods of time INFECTS OLD RBCs

Incubation Period : 

Incubation Period P. Falciparum 12 days P. Vivax 14 days* P. Ovale 14 days* P. Malariae 30 days * May be 8 - 10 months or longer for some strains

Acute Symptoms : 

Acute Symptoms Classical cyclic paroxysm: Cold stage: chills and shaking Hot stage: warm, headache, vomiting Sweating stage: weakness Feel well for period of time, then cycle repeats itself

Presentation : 

Presentation Fever 96% Chills 96% Headache 79% Muscle Pain 60% Palpable liver 33% Palpable Spleen 28% Nausea or vomiting 23% Abdominal pain/diarrhea 6%

Complicated Malaria : 

Complicated Malaria Hyperparisitemia: (>3%) Hypoglycemia: (<60 mg/dl) Severe anemia (hct < 21% or rapidly falling hct) Renal failure Hyponatremia Cerebral malaria Prolonged hypothermia High output vomiting or diarrhea Pregnancy

Signs In Acute Infection : 

Signs In Acute Infection Slightly ill to in distress Alert to unconscious Fever

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Gold standard: Multiple thick and thin smears Dip stick tests CBC Anemia Leukopenia, or leukocytosis No eosinophilia DIAGNOSIS

Treatment : 

Treatment CHLOROQUINE sensitive infections: CHLOROQUINE 600 mg (2 tabs) P.O. initially 300 mg (1 tab) in 6 hrs 300 mg (1 tab) QD for 2 days

Treatment : 

Treatment Uncomplicated CHLOROQUINE-resistant infections: Quinine 650 mg PO TID x 3 days and DOXYCYCLINE 100 mg PO bid x 7 days, OR MEFLOQUINE 1000-1500 mg PO once Complicated or severeinfections I.V. QUINIDINE or quinine

Treatment : 

Treatment VIVAX and OVALE therapy should include PRIMAQUINE 15mg PO QD x 14 days CDC now recommends: PRIMAQUINE 30mg PO QD x 14 days

Optimal Treatment Approach : 

Optimal Treatment Approach Rapid case identification Rapid PARASITOLOGICAL classification Rapid initiation of therapy Rapid initiation of supportive care

Control Of Malaria : 

Control Of Malaria Global eradication efforts by WHO in 1950s Efforts now focus on CONTROL vs ERADICATION

Points Of Attack : 

Points Of Attack 1. Attack the parasite in the human host 2. Reduce contact between humans and mosquitoes 3. Decrease mosquito population

Attack The Parasite In The Human Host : 

Attack The Parasite In The Human Host Treat malaria infections with effective medications Use prophylactic drugs to prevent illness and/or infection

Attack The Parasite In The Human Host : 

Attack The Parasite In The Human Host Chemoprophylaxis is based on current drug resistance patterns MEFLOQUINE first line prophylaxis Mefloquine 250 mg po q week, 1-2 wks prior to 4 wks after DOXYCYCLINE as second line drug Doxy 100 mg po qd, 2 days prior to 4 wks after PRIMAQUINE 30 mg* po qd x 14 days terminal prophylaxis *15 mg per FDA and drug product information insert

New Antimalarial for Prophylaxis: Atovaquone/Proguanil (Malarone®) : 

New Antimalarial for Prophylaxis: Atovaquone/Proguanil (Malarone®) Licensed July 2000 in USA for treatment and prophylaxis of P. falciparum Atovaquone is a blood schizonticide Proguanil is metabolized to cycloguanil, a tissue schizonticide Combination very effective for treatment of multi-drug resistant P. falciparum Generally well tolerated with >95% efficacy vs. placebo

Dosage of Malarone® : 

Dosage of Malarone® Prophylaxis dose: one tablet per day Start 1-2 days prior to entering endemic area Continue for one week after leaving (causal prophylaxis, kills parasites in liver) Adult formulation: 250 / 100 mg atovaquone / proguanil in single combination tablet Pediatric formulation: 62.5 / 25 mg single tablet

Who Should Use Malarone® for Prophylaxis? : 

Who Should Use Malarone® for Prophylaxis? Persons on short trips who wish to avoid a long course of medication after return Persons concerned about drug side effects Persons traveling to areas where resistance to other drugs may occur Persons who prefer a daily regimen

Reduce Contact Between Humans And Mosquitoes : 

Reduce Contact Between Humans And Mosquitoes Personal protective measures Proper wearing of uniform DEET PERMETHRIN Bed nets

Reduce Contact Between Humans And Mosquitoes : 

Reduce Contact Between Humans And Mosquitoes Personal protective measures Proper wearing of uniform DEET PERMETHRIN Bed nets

Slide 36: 

Decrease Mosquito Population Surveillance of mosquito populations Identify and eliminate breeding sites Proper insecticide application Attack larval stages Attack adult mosquito

Slide 37: 

48 cases in country 83 cases following return from deployment 62 US Army 21 USMC 77% of cases due to P. vivax Somalia: 1992-3

Somalia Lessons Learned : 

Somalia Lessons Learned Issues Command responsibility Compliance: switch to MEFLOQUINE Location of camps Weather ? poor usage of DEET Non-use of bed nets PRIMAQUINE terminal prophylaxis USA had not recommended

Slide 39: 

Cases resulted from failure to implement proper prophylaxis and personal protection Mefloquine more effective than Doxycycline in USMC Somalia Conclusions

Command Responsibility : 

Command Responsibility Field Marshall Sir William Slim: “If the overall result was less than 95% positive, I sacked the commanding officer. I only had to sack three; by then the rest had got my meaning.” Sir Neil Cantlie, Dir Gen Brit Army Med Services: “When for the first time in history a combatant officer was considered unfit to command a unit on the grounds that he had allowed his men to become ineffective through disease, a new day in military medicine dawned. The clouds of forgetfulness must not be allowed to overshadow the brightness of that day.”

Slide 41: 

Conclusions Education and aggressive monitoring of compliance is needed for chemoprophylaxis and personal protective measures to work

Malaria Outbreak Among Members of JTF LiberiaConsensus Conference Report : 

Malaria Outbreak Among Members of JTF LiberiaConsensus Conference Report 9 October 2003

Slide 43: 

Contents of Brief Background Information 3 -6 Questions, data and answers: 1. Was there a problem with the availability of mefloquine? 7 2. Was there a problem with generic medication’s potency or formulation? 8 3. Were Marines taking mefloquine according to requirements 9 4. Was the malaria parasite resistant to mefloquine? 10 5. Was DEET available for use? 11 6. Were permethrin-treated utilities available for wear? 12 7. Were bed nets used? 13 8. Was local insect control adequate? 14-15 9. Were the medical staff adequately trained in diagnosis and management of malaria? 16-17 10. Can U.S. Forces deploy to high-risk areas and not suffer similar malaria outbreaks? 18 Recommendations 19-20 Continuing and Future efforts 21-22 Organizations Represented 23

Background:Recent Historical Experience : 

Background:Recent Historical Experience Somalia – 1993 106 Marine cases 127 U.S. Army cases Sierra Leone –1996 6 Marine cases 91 British Army cases Navy/Marines 1997-2000 - 62 cases worldwide Nigeria – 2001 7 cases with 2 deaths, U.S. Army Special Forces

Background:JTF Liberia Outbreak : 

Background:JTF Liberia Outbreak Total of JTF spending any time ashore – 290 Quick Reaction Force – 225 MEU personnel surveyed during investigation - 157 80 cases treated: 51 cases smear positive 29 cases diagnosed by clinical criteria 1 civilian, 1 U.S. Army, 7 U.S. Navy, 2 FAST Marines, 69 Marines of 26th MEU

Background:JTF Liberia Outbreak : 

Background:JTF Liberia Outbreak AFMIC Risk Assessment for Liberia Historical predicted malaria attack rate: 11-50% risk for unprotected personnel Actual Liberia experience: 44% attack rate (69/157) for 26th MEU personnel spending nights ashore 28% attack rate (80/290) for JTF members spending any time ashore

Background:Pre-deployment Analyses and Intelligence : 

Background:Pre-deployment Analyses and Intelligence Liberia known to be highest risk area for multiple vector-borne diseases Humanitarian Assistance Survey Team, JUL 03: limited in scope assessed infrastructure, public health, sanitation, and security threats focused on future civilian relief efforts vice deploying forces JTF-L OPORD preventive measures consistent with survey, intelligence and recommendations from AFMIC, CDC and WHO

1. Was there a problem with the availability of mefloquine? : 

1. Was there a problem with the availability of mefloquine? Mefloquine dispensed to Marines Verified by survey Verified by presence of tablets in Marines’ pockets upon arrival at NNMC Bethesda Verified by presence of mefloquine in serum samples MEU members were taking mefloquine prior to entering Liberia Verified by mefloquine metabolite levels ANSWER: No. Mefloquine was readily available

2. Was there a problem with the potency or formulation of generic mefloquine? : 

2. Was there a problem with the potency or formulation of generic mefloquine? Mefloquine met all FDA requirements. Tablets removed from Marines’ pockets produced predicted blood levels in test subjects. Chemical analysis by FDA within standards. FDA recommends continued use of current generic mefloquine formulation. ANSWER: No. Mefloquine potency and formulation was adequate.

3. Were Marines taking mefloquine according to requirements? : 

3. Were Marines taking mefloquine according to requirements? Steady-state ratio of mefloquine metabolite (MMQ) present in 93 of 133 indicating past use Protective mefloquine (MQ) levels present in 19 of 133 specimens indicating recent use Only 7 of 133 had both protective MQ and adequate MQ/MMQ ratio. Inadequate levels noted despite the survey indicating 95% of Marines claimed no missed doses. ANSWER: No. Lab data indicates inadequate compliance with required dosing schedule.

4. Was the malaria parasite resistant to mefloquine? : 

4. Was the malaria parasite resistant to mefloquine? Testing at Walter Reed Army Institute for Research did NOT reveal clinically significant resistance Consensus remains that mefloquine is the drug of choice for Liberia ANSWER: No. Resistance not a factor.

5. Was DEET available for use? : 

5. Was DEET available for use? 290 personnel surveyed. DEET use: Possession of DEET was a repeated inspection item. 79/290 (27%) used some type of repellant at least once. Only 19 of these used 12-hour DoD-issued DEET formulation. Majority used less-effective non-DoD supplied or non-DEET repellant. ANSWER: Yes. Long-acting DEET was available, but not routinely used. Other DEET formulations were more commonly used though less effective as repellants.

6. Were permethrin-treated uniforms available for wear? : 

6. Were permethrin-treated uniforms available for wear? 290 personnel surveyed: 36 (12%) wore permethrin-treated utility uniforms ashore Unable to obtain bulk permethrin for treatment, only aerosol available aboard ship Only desert utilities were treated by aerosol prior to deployment Woodland utilities worn ashore, appropriate to local environment Aerosol spray can is the least effective method available for treatment ANWER: No. Few adequately treated uniforms available for use ashore in Liberia.

7. Were bed nets used? : 

7. Were bed nets used? Bed nets not carried ashore due to: Weight restrictions No cots to hold poles Sleeping on paved/hard surface precluded pole use Assumed short stay with minimal exposure Current issue bed net system requires soft surface for poles or cot to effectively deploy ANSWER: No. Not used due to net design and mission requirements.

8. Was local insect control adequate? : 

8. Was local insect control adequate? ANSWER: No. Local control for malaria vectors not feasible given broad distribution, and limited ARG/MEU capabilities.

8. Was local insect control adequate?- Background : 

8. Was local insect control adequate?- Background Requirements to analyze and implement insect control exceeded ARG/MEU capabilities Minimal mosquito abatement equipment routinely carried with ARG/MEU No mosquito abatement expertise routinely included in ARG/MEU Table of Organization (T/O) Analysis requires: Traps and microscope Expertise to count and identify species Site survey following outbreak revealed: Mosquito risk widely and equally spread across region Large local human reservoir of malaria Highly mobile mosquito species, routinely flies > 1 mile to feed

9. Was the medical staff adequately trained in diagnosis and management of malaria? : 

9. Was the medical staff adequately trained in diagnosis and management of malaria? ANSWER: No. Routine pre-deployment training does not include infectious disease refresher for physicians or lab techs.

9. Was the medical staff adequately trained in diagnosis and management of malaria? - Background : 

9. Was the medical staff adequately trained in diagnosis and management of malaria? - Background Recent formal training for one physician, who established initial diagnosis and implemented treatment No laboratory technicians had recent formal training No formal pre-deployment refresher training received Early diagnosis and treatment decreases morbidity and mortality in malaria Treatment requires medications not used for prophylaxis and not routinely included in AMAL

10. Can U.S. Forces deploy to highly malarious areas, without suffering similar malaria outbreaks? : 

10. Can U.S. Forces deploy to highly malarious areas, without suffering similar malaria outbreaks? Current procedures for personal protective measures effective Current chemo-prophylaxis effective Currently complex regimen makes implementation difficult ANSWER: Yes. Present measures, if applied to and by each individual ground force combatant, are adequate to prevent malaria in Liberia and other high-risk areas.

Recommendations: Near Term : 

Recommendations: Near Term Provide USMC-wide guidance requiring: Permethrin treatment for all uniforms and bed nets prior to deployment using best available techniques Use only DoD sustained-release DEET or DEET/Sunscreen formulations Provide routine tropical medicine refresher training to MEU medical staff during pre-deployment work-ups Add Malarone and oral quinine medications to AMAL Operational planners and chain of command emphasize awareness/assessment of infectious disease threat Improve training and equipment of ARG/MEU Preventive Medicine technicians to enhance insect control capability

Recommendations: Long-term : 

Recommendations: Long-term Permethrin treat uniforms at the factory during procurement Procure and distribute improved mosquito net system as USMC standard issue When OPLANS indicate potential for entry into high malaria-risk area, obtain and assure ARG/MEU capability for continuous onsite assessment and abatement of health threats

Medical Continuing Efforts : 

Medical Continuing Efforts Malaria antibody testing of blood samples Continue ongoing monitoring for emerging permethrin resistance in mosquitoes Continue evaluation of malaria parasites for mefloquine resistance

Medical Research and Development : 

Medical Research and Development Field-use malaria test kit “Fire-and-forget” solutions to reduce complexity: Support malaria vaccine research Support malaria medication research

Organizations Represented : 

Organizations Represented Food and Drug Administration Centers for Disease Control and Prevention World Health Organization Walter Reed Army Institute for Research Naval Medical Research Center Armed Forces Medical Intelligence Center U.S. Air Force Medical Support Agency Joint Chiefs of Staff - J4 Uniformed Services University of the Health Sciences Naval Medical Education and Training Command DoD Global Emerging Infections System Marine Forces, Atlantic II Marine Expeditionary Force National Naval Medical Center Naval Environmental Health Center Naval Environmental and Preventive Medicine Unit – Sicily Headquarters, Marine Corps, PP&O Commander Amphibious Task Force Marine Expeditionary Unit 26 Navy Disease Vector Ecology and Control Center Naval Forces Europe Joint Task Force - Liberia U.S. Army Medical Research and Materiel Command U.S. Navy Bureau of Medicine and Surgery Headquarters, Marine Corps, Health Services U.S. Army Office of the Surgeon General

July 20, 2001 / 50(28);597-9 : 

July 20, 2001 / 50(28);597-9 Malaria Deaths Following Inappropriate Malaria Chemoprophylaxis January-March 2000: two U.S. citizens died of malaria due to inappropriate chemoprophylaxis 12 y/o, 3 weeks Nigeria, took chloroquine 47 y/o, 11 days E.. Africa, took chloro/proguanil 4685 cases of malaria in U.S. travelers from 1992 - 2001 893 (19%) inappropriate chemoprophylaxis 2616 (56%) took no chemoprophylaxis Among persons who took inappropriate chemoprophylaxis, 70% took chloroquine for travel to area with known chloroquine resistance (1995 - 2001)

Malaria! : 

Malaria! Remember: Flu-like Symptoms + ‘Recent’ Hx Travel To Malarious Area = Think Malaria

Summary : 

Summary Mosquito-borne infectious disease Tropics, subtropics P. falciparum, vivax, ovale, malariae Incubation period nearly two weeks Cyclic paroxysms Fever Thick and think blood smears for diagnosis

Summary : 

Summary Drug resistance is increasing Chemoprophylaxis can prevent infection Carefully screen people when prescribing mefloquine Great importance of personal protective measures Aggressive monitoring needed to enforce ppm at command level Regard and manage malaria as medical emergency

Questions? : 

Questions?