Neglected Tropical Diseases II

Tissue Nematodes (roundworms)

Tissue nematode infections

1. Lymphatic filariasis
2. Subcutaneous tissues / eyes
3. Guinea worm infection
4. Onchocerciasis
5. Loa loa
6. Toxocariasis

– Albendazole plus ivermectin; or

– Albendazole plus diethyl-carbamazine

(DEC)

– Surgery eg. hydrocoele

– Mass administration of medication

– Vector control (mosquito)

– Personal protection from vector eg.

mosquito nets

Launched by WHO in 2000

1. Interruption of transmission
   1. mass administration to at-risk population annually for at least 5 yrs;
2. Alleviation of morbidity + education programmes
3. Elimination by 2020

• 99% of cases found in 31 sub-Saharan and central African countries
• Small minority reported in South/Central America: Brazil, Mexico, Venezuela.
• Elsewhere: Yemen
• Progress in eradication: Columbia in 2013 & Ecuador in 2014 declared free of onchocerciasis

• Onchocerca volvulus

• Transmitted by repeated bites of infected blackflies (Similium spp)

Demonstration of microfilariae in skin or corneal samples or adult worms in nodule biopsy sample

Clinical features

Movement of microfilariae through tissues causing intense inflammatory reaction

Disease mainly of eye and skin:

• Initial nodule
• Itchy erythematous rash
• Chronic lymphadenopathy with lymphoedema

Second leading infective cause of blindness

Worldwide – est. 1 million cases blindness or visual impairment

Impact

In Africa: > 600,000 DALYs lost per annum

Diminished productivity (esp. agriculture)

• Due to actual disability
• Abandonment of cultivable land eg. fertile areas near rivers

• keratitis with corneal fibrosis
• Other possible ophthalmic complications: iridocyclitis, glaucoma, choroiditis, etc.

• Other effects: weight loss, severe pruritus

• ivermectin annually x 10-15 yrs (WHO recommendation)

Prevention:

• Personal protective clothing
• Application of larvicides to blackfly breeding grounds
• Mass application of ivermectin

(West Africa) 1974-2002:

• Insecticide against blackfly larvae
• Ivermectin mass medication
• 40 million treated
• Blindness prevented in 600,000
• 25 million hectares of land reclaimed for settlement and agriculture

• Biannual large-scale population Rx with ivermectin
• Reported cessation of transmission in Columbia (2007), Ecuador (2009), Mexico, Guatemala (2011)

African Programme for Onchocerciasis Control (APOC) (1995 – )

• Large-scale Rx and vector control
• 2013: > 100 million Rx in 24 countries (>75% therapeutic coverage for the disease)

• Involvement of a snail as intermediate host
• Geographic distribution varies widely according to type of fluke
• Most flukes can be treated with praziquantel

• Often co-endemic with soil-transmitted helminth infections

Schistosomiasis (snail fever)

Urogenital schistosomiasis:

S. haematobium: Africa, Middle East; worms located in venules of lower urinary tract

Intestinal schistosomiasis

worms located in mesenteric venules

S. japonicum / S. mekongi (Asia); S. mansoni (S. America, Africa)

>200 million cases; >90% cases in sub-Saharan Africa: up to 300,000 deaths per annum in sub-Sahara

• Highest incidence in children, teenagers, young adults

Impact

1.7 – 4.5 Million DALYs lost per annum

Likely to be higher (secondary effects eg. anaemia, growth/cognitive impairment often not taken into account)

Diagnosis

1. Serology
2. Microscopy for eggs in stools, urine, or tissues.
3. Proctoscopy or cystoscopy
4. Radiological imaging

• Prickling sensation; itchy maculopapular rash

Acute schistosomiasis:

2-8 wks after exposure & lasts few wks:

• Fever, chills, headache, abd pain, diarrhoea, sometime pulm symptoms
• Eosinophilia
• Genital sores/ulcers

Other consequences:

• Female genital schistosomiasis: 3-fold increased risk of HIV acquisition
• Liver failure, portal hypertension
• Bladder cancer

May have no or mild symptoms with light infections

Severe infections:

S. japonicum/S. mansoni/S. mekongi:

• Fatigue, abd pain, diarrhoea, splenomegaly;
• Anaemia, malnutrition, growth/cognitive impairment
• Liver fibrosis, portal hypertension

S. haematobium:

• Haematuria, dysuria, fibrosis & calcification of bladder

i) Avoid exposure to contaminated waters
ii) Provision of safe drinking water
iii) Proper sanitation & disposal of human & animal waste

iv) Control of snail populations (often difficult)
v) Health education

• Preventive chemotherapy: mass treatment with praziquantel in endemic areas
• Morbidity control: mass treatment of high-risk groups eg. school children, pregnant women, occupational risks.

• Many mammalian animals are the natural reservoir
• Endemic in 21 Latin American countries

Other modes of transmission: consumption of contaminated food; transfusion of contaminated blood/organs; vertical transmission, etc.

Triatomine bug:

• Lives in crevices of poorly constructed houses
• Active mostly at night
• Blood meal → bites exposed areas of skin
• Defaecates after blood meal
• T.cruzi in faeces contaminates skin breaks

About 7 million people affected globally, mostly Latin America

About 10,000 die from Chagas-related complications

• Rural settings
• Suboptimal human dwellings

Acute Chagas’ Disease

Chronic Chagas’ Disease

• Muscles including myocardium
• GI smooth muscles: oesophagus & colon

Presents 2 mths after infection

Symptoms often mild & non-specific

• Chagoma
• Fever, malaise, anorexia, oedema, myalgia, lymphadenopathy, etc.

Occasional: meningoencephalitis; myocarditis

10-30% chronic infections result in symptomatic disease (30% CVS; 10% GIT)

Chronic symptoms manifest after yrs or decades after initial infection

• Heart failure (usu right-sided); arrhythmias
• Dysphagia, odynophagia, aspiration, etc.
• Chronic constipation, abd pain, obstruction, etc.

• Stigmatisation – rural poor disproportionately affected: disease associated with poverty and social exclusion
• Employment prospects, access to medical help, social rejection
• Misconceptions about disease due to lack of education etc.

• Clinical / epidemiological
• Acute disease: examination of blood film
• Chronic disease: IgG detection
• PCR?

Treatment:

Nifurtimox (90-120d), benznidazole (60d): very effective during acute infection

Indicated for acute phase, early phase in chronic infection, reactivated disease in immunosuppressed patients, infants with congenital disease

• Improvement of living conditions
• Improved sanitation and better infrastructure to prevent vector infestation

• Vector control: spraying of insecticides home & surrounding environment
• Personal and food hygiene; use of bed nets
• Screening of donor blood and organs

• No vaccine available; control of reservoirs very difficult

• Emergence in previously disease-free regions eg. Amazon basin

• Persistence of disease in spite of control measures eg. Bolivia

• Increased mobility of populations from Latin American countries to rest of world

T. brucei gambiense:

• primarily infects wild game; occasionally humans;
• Vectors found in tropical rainforests of Central and West Africa

T. brucei rhodesiense:

• primarily infects humans;
• Vectors found in savanna & woodlands of East Africa

Epidemics: last one from 70s-90s

T. b. gambiense (chronic infection)

Endemic in 24 countries

(West/Central Africa)

Constitutes 98% cases of trypanosomiasis

T. b. rhodesiense (acute infection)

Endemic in 13 countries

(East/Southern Africa)

2-3% cases of trypanosomiasis

1. Initial trypanosomal chancre
2. Proliferation in lymphatic system; spleen and cardiac involvement (haemo-lymphatic stage; stage I)
3. Crosses blood-brain barrier into CNS (meningo-encephalitic stage; stage II)

• Chancre fluid
• Blood film

• CSF analysis
  • Pleocytosis
  • Raised protein
  • Raised pressure

• Painful chancre

Wks/mths later:

• intermittent fever, lymphadenopathy, hepatosplenomegaly, erythematous rash

Stage II:

• meningoencephalitis: headaches, irritability; progressive somnolence and restlessness;
• ataxia, slurred speech; coma & death

• More acute course

Onset of symptoms within days/wks

• Fever, headache, rash
• Lymphadenopathy not a prominent feature
• Arrhyhmias/congestive heart failure (pancarditis)
• CNS disease (wks to mths)

Stage I Stage II

Pentamidine; Melarsoprol;

Suramin Eflornithine;

Nifurtimox

Public-private partnerships in supplying meds to endemic countries

Progress

Significant drop in no. of new cases (73%) from 1999 to 2012

• WHO target: elimination of African trypanosomiasis as a public health problem by 2020.

• Reducing disease reservoir: effective diagnosis and treatment
• Vector control: insecticides against tsetse flies

• Education: measures to reduce exposure: long-sleeved shirts, medium-wt materials, use of insect repellant, insect screens, bed nets, etc.

• Globally affects about 12 million people; disease has spread considerably in the past decade

Around 1 million new cases annually, and 20,000-30,000 deaths annually

Socioeconomic: poor housing and sanitation, overcrowding, population displacement, poverty

Health: malnutrition; HIV co-infection (↑ risk of VL by 100-2000 times)

Environmental: living near forested areas; associated with deforestation, dam-building, irrigation schemes

Cutaneous Leishmaniasis (CL)

• 0.7-1.2 million new cases every year (>2/3 in 6 countries incl. Afghanistan, Brazil, Iran, Syria)

1/3 cases from each of 3 regions:

• Middle East (eg. Afghan, Iran, Syria)
• S. America (Brazil, Peru, Colombia, Bolivia)
• Mediterranean (Algeria, Morocco, Turkey)

Plus pockets in Africa and Latin America

Skin lesions: ulcers: usually appear few wks/mths after bite of sandfly

Ulcerative skin lesion, mucosal destruction

Diffuse cutaneous leishmaniasis (R): diffuse nodular skin lesions sometimes mimicking leprosy

Mucocutaneous leishmaniasis: eg. nose, mouth, throat

90% in Brazil, Bolivia, Peru

Endemic in >60 countries (Indian subcontinent and east Africa);

• 200,000-400,000 new cases of VL: 90% in India, Bangladesh, Sudan, South Sudan, Ethiopia, Brazil

If untreated, typically progressive and almost uniformly fatal

VL (kala azar): typically takes 2-8 mths to develop

• hepatosplenomegaly (especially spleen), lymphadenopathy, bone marrow (pancytopenia or thrombocytopenia), fever, wt loss, anorexia
• Some pts: HIV co-infection

Demonstration of Leishmania (amastigotes) in tissues or aspirates eg. bone marrow or lymph node ie. Leishman-Donovan bodies

Others eg. PCR

Prevention

Personal protection: clothing; bed nets (NB!); insect repellant; screened windows; etc.

Minimise outdoor activities after dusk (sandflies most active during this period)

Vector control: spraying of insecticides for living/sleeping areas; control of breeding areas; general hygiene/sanitation measures

• Facilitate early diagnosis and treatment
• Vector control of sandfly populations
• Provision of health education and training materials
• Disease surveillance: early detection and containment of epidemics
• Early diagnosis and effective management of Leishmania and HIV co-infection

• Hosts: poverty; malnutrition; HIV co-infection; increased mobility

• Vectors: poor sanitation; overcrowding; climate change
• Reservoirs: humans and animals

Drug therapy – treatment of individuals and reduction in human reservoir

• 4 drugs can treat 7 most common NTDs: albendazole, praziquantel, ivermectin, azithromycin

• Est. costs: $0.40-0.80 per person per year. Low cost; huge public health impact

• Intensive/aggressive disease management: diagnosis/Rx
• Large-scale preventive chemotherapy

• Vector ecology and management
• Veterinary public health services
• Provision of safe water, sanitation and hygiene (WASH)