+ ZIKA

Background Zika virus is a member of the genus flavivirus (closely related to dengue, yellow fever, Japanese encephalitis and West Nile viruses) whose primary vector is the Aedes aegypti mosquito (1). Originally identified in Uganda in 1947 in monkeys, Zika was found in humans in 1952 (2).

Transmission can occur in multiple ways, the following ways are the most common:

Bite of an infected mosquito Maternal-fetal transmission Sex Blood transfusion Organ transplantation Laboratory exposure (3)

Clinical Presentation Common signs and symptoms of the Zika virus include fever, rash, joint pain, conjunctivitis, myalgias and headache. Symptom onset is unclear but is most likely to be a few days and can last from days to weeks (1). 80% of patients exposed to the virus are asymptomatic, but those that are affected will mostly have mild symptoms. Severe complications seem to be rare. Microcephaly in infants born to mothers infected with the virus during pregnancy and Guillain-Barre syndrome are the most serious complications (2)

Testing The CDC recommends testing for pregnant females who have traveled to areas with active Zika transmission with concern for the infection. Sexual transmission is possible and the CDC recommends testing for those that may have been exposed to Zika through sex having symptoms. Testing men is not recommended to determine if Zika will be transmitted sexually (1). The World Health Organization has expanded the patients that should be tested to include:

Patients with sexual contact with a confirmed or probable case Patients who meet the case definition of a suspected case with neurological disorders Pregnant women with a history of travel to areas with ongoing Zika virus transmission and/or sexual contact with a confirmed or probable case Pregnant women from areas with ongoing Zika virus transmission whose fetuses are known, or suspected to have, congenital brain abnormalities Neonates with microcephaly or neurological abnormalities born in areas with ongoing Zika transmission or born to women with a history of travel to a Zika-affected area during pregnancy Infants with mothers diagnosed with Zika virus, especially if breastfeeding Stillbirths or spontaneous abortions from women who have lived in or travelled to a Zika-affected area during the pregnancy (2) Couples/women planning on pregnancy should use protection or abstain from sexual intercourse for at least 8 weeks. If men are symptomatic they should adopt safe sex practices for at least 6 months2 as the Zika virus can be present in semen for up to 93 days after onset of illness (3) Testing that is available include nucleic acid testing (NAT) via RT-PCR. Whole blood, serum or urine can be obtained as long this is within 7 days of symptom onset. Serology examining IgM requires whole blood or serum <5 data-preserve-html-node="true" days of symptom onset. The test needs to be repeated 2-3 weeks later for confirmation (2). For patients being tested >7 days after symptom onset, the preferred method is serology (IgM) testing.

Treatment Symptomatic treatment is the only recommendation at this point:

Get plenty of rest Drink fluids to prevent dehydration Take medicine such as acetaminophen to reduce fever and pain Do not take aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) If you are taking medicine for another medical condition, talk to your healthcare provider before taking additional medication (1) Prevention No vaccinations have been approved to date but research is continuing. There is currently a phase I clinical trial in process through the NIH to determine if an immune response will occur with this vaccine.4 Prevention of Zika will be extremely important for people concerned about transmission. The CDC has come up with a list of ways to prevent the transmission that are as follows:

Wear long-sleeved shirts and long pants when in endemic areas Stay in places with air conditioning and window and door screens to keep mosquitoes outside Take steps to control mosquitoes inside and outside your home Treat your clothing and gear with permethrin or buy pre-treated items Use Environmental Protection Agency (EPA)-registered insect repellents. Always follow the product label instructions When used as directed, these insect repellents are proven safe and effective even for pregnant and breastfeeding women Do not use insect repellents on babies younger than 2 months old Do not use products containing oil of lemon eucalyptus or para-menthane-diol on children younger than 3 years old Mosquito netting can be used to cover babies younger than 2 months old in carriers, strollers, or cribs to protect them from mosquito bites Sleep under a mosquito bed net if air conditioned or screened rooms are not available or if sleeping outdoors Prevent sexual transmission of Zika by using condoms or not having sex (1)

References

The Center for Disease Control. Zika Virus http://www.cdc.gov/zika. Aug 4 2016.

World Health Organization. Zika Virus. http://www.who.int. June 2 2016.

LaBeaud, A. Zika Virus Infection: an Overview. http://www.uptodate.com/contents/zika-virus-infection-an-overview. Aug 4 2016.

The National Institute of Health. Zika Virus. https://www.nih.gov/news-events/news-releases/nih-begins-testing-investigational-zika-vaccine-humans. Aug 3 2016.

+ Giardia

Background A protozoan parasite capable of causing infectious diarrheal disease and is a significant cause of morbidity and mortality as a waterborne or foodborne illness for international travelers. It infects nearly 35% of people in developing countries and is the most common intestinal parasitic disease affecting humans.

Clinical Presentation Flatulence Nausea/Vomiting/Diarrhea Foul smelling stools Steatorrhea Abdominal cramps Dehydration Weight loss Failure to thrive Prevention

Good hygiene (before preparing food, eating, caring for patients, after using the toilet) Minimize contact with animal feces as it is transferable between animals and humans Drink safe water Bottled water Drinks with no ice Boil water for at least 10 minutes Use a filter (NSF 53 or 58 filter for cyst and oocyte reduction) Treatment

Symptoms usually resolve in 5-7 days with treatment

Pregnancy

Keep patient hydrated and attempt to defer treatment until after first trimester Paromomycin can be used Avoid metronidazole or tinidazole Breast Feeding

Mebendazole and Paromomycin are ok for breastfeeding mothers Tinidazole and Metronidazole are contraindicated Unknown effects with nitazoxanide or albendazole

Article by Julie Teuber, MD

References

Prevention and Treatment of Giardia. Uptodate. Accessed July 2016. Giardia. CDC

Granados CE, Reveiz L, Uribe LG, Criollo CP. Drugs for treating giardiasis (Review). Cochrane Database Syst Rev. 2012;12

Tinidazole Drug Information. UptoDate. Accessed July 2016

Centers for Disease Control (CDC). Neonatal deaths associated with use of benzyl alcohol—United States. MMWR Morb Mortal Wkly Rep. 1982;31(22):290-291.

+ H Pylori

Background

US - The Helicobacter pylori prevalence in the US is estimated to be 32% with a disproportionate amount affecting low income African Americans and Whites. Infection, transmitted the fecal-oral route, increases risk for both gastric and duodenal ulcers, gastric lymphoma and cancer, and GI bleeding. In a prospective cohort of over 80,000 patients in the Southern Community Cohort Study (across 12 states in the South East), serum studies were performed indicating that 89% of low income African Americans and 69% of low income whites were infected or had previously been infected with H pylori (serology testing doesn’t necessarily indicate active infection). Odds ratio for African Americans to be infected compared to Whites was 3.5. This inverse association with socioeconomic status and H pylori infection has been replicated across studies and is likely reflected in our EDs.

Developing Countries - H pylori affects approximately 50% of the world’s population. That is an estimated 3.5 billion people, with prevalence average 60% in Central America and reaching as high as 90% in many parts of Africa and Asia. Some experts purport that the only way to address it large scale is by creating vaccines, which are currently under investigation.

Current guidelines American College of GI (updated 2005)

In populations where H pylori is >10%, test and treat is preferable to empirical PPI.
Logic would carry that when practicing internationally, test and treat given the high disease burden If patient is failing a PPI, use Urea Breath Testing (UBT) before endoscopy In populations with high H pylori prevalence, 40% of patients positive via UBT had duodenal ulcers and only 2% negative via UBT had ulcers Level of evidence for empiric PPI and 'Test and Treat' are both level A 'Test and Treat' is cost effective vs PPI with endoscopy Note that serologic testing is, in general, a poor option as it has lower sensitivity and may remain positive after the patient has cleared any active infection

Treatment Eradication of Helicobacter pylori is associated with healing of ulcers as well as decreased risk of future ulcers and healing. Meltzer et al recently studied the utility of the C13 Urease breath test out of the emergency department and found a prevalence of 25% active H pylori infections. These patients were tested and given triple therapy for H pylori. This took place at George Washington University and a study is currently underway to follow the symptoms of the patients who were tested and treated.

The key to treatment is compliance for the full regimen. Triple therapy and quadruple therapy often cause significant nausea, but stopping treatment early causes high rates of bacterial resistance.

Written by Tyler Winders, MD

References

Meltzer AC, Pierce R, Cummings DA, Pines JM, May L, Smith MA, Marcotte J, McCarthy ML. Rapid (13)C Urea Breath Test to Identify Helicobacter pylori Infection in Emergency Department Patients with Upper Abdominal Pain. West J Emerg Med. 2013 May;14:278-82.

Epplein M, Signorello LB, Zheng W, Peek RM Jr, Michel A, Williams SM, Pawlita M, Correa P, Cai Q, Blot WJ. Race, African ancestry, and Helicobacter pylori infection in a low-income United States population. Cancer Epidemiol Biomarkers Prev. 2011 May;20:826-34.

Delaney BC, Qume M, Moayyedi P, Logan RF, Ford AC, Elliott C, McNulty C, Wilson S, Hobbs FD. Helicobacter pylori test and treat versus proton pump inhibitor in initial management of dyspepsia in primary care: multicentre randomised controlled trial (MRC-CUBE trial). BMJ. 2008 Mar 22;336:651-4.

Talley, Nicholas. "Management of Dyspepsia." American College of Gastroenterology. Am J of Gastroenterology, 2005. Web. 21 Aug. 2014.

+ Malaria

Background

Malaria is a mosquito-borne infectious disease commonly transmitted via a bite from an infected female Anopheles mosquito. The disease is widespread in tropical regions surrounding the equator. There are five species of Plasmodium and the vast majorities of deaths are caused by P. falciparum. There were 198 million documented cases of malaria in 2013 and as many as 1.2 million people died (WHO). Most deaths occur in children under the age of 5, and it is estimated that a child dies of malaria every 30 seconds. Other high risk groups include pregnant women and non-immune travelers. Malaria is commonly associated with poverty and is a potential barrier to economic growth, accounting for nearly 40% of public health expenditure in Africa.

Clinical Presentation

Signs/symptoms of malaria typically begin 8-25 days following infection. Patients often initially develop flu-like symptoms. Presentation may include fever (often cyclical), headache, rigors, arthralgias, nausea/vomiting. Findings include hemolytic anemia (sometimes severe), splenomegaly, jaundice, hemoglobinuria (aka “Blackwater Fever with renal failure), and jaundice. Cerebral malaria is defined as severe P. falciparum-malaria presenting with neurologic symptoms, including coma or seizure, and is often fatal. Severe malaria can progress rapidly and mortality is as high as 20% despite aggressive management.

Diagnosis

There are no pathognomonic clinical signs or symptoms for the diagnosis of malaria. The gold standard is visualization of parasites in stained samples—3 sets of Giemsa thick & thin blood smears. In resource-limited settings (such as Shirati), Rapid diagnostic tests (RDTs), detecting antigens or antibodies, are more common and very useful.

Treatment

Most effective treatment is with use of artemisinins in combination with other antimalarials (amodiaquine, lumefantrine, mefloquine, or sulfadoxine/pyrimethamine). We commonly used artemisinin-lumefantrine (Coartem) for outpatient treatment in Tanzania. For severe cases and inpatient management we used IV quinine therapy as well.

Prophylaxis

Multiple regimens including chloroquine (extensive resistance), mefloquine, doxycycline, and Malarone (atovaquone-proguanil HCl) can be used.

Shirati clinical Case

13 year old-male with no significant medical history presents with 3 days of fever, cough, chest pain, and intermittent nose bleeds. He denies nausea, vomiting, diarrhea, or abdominal pain. His cough is non-productive and he has had no sick contacts.

T 39.1C HR 98 BP 110/70 RR 16 weight 40kg Generally he is a mildly ill-appearing with skin that is warm to touch. He has mild conjunctival pallor with a clear oropharynx without erythema or lesions. Cardiovascular exam with S1 S2 present, borderline tachycardia, regular rhythm, no murmurs. He has no respiratory distress with good air movement and diffuse mild expiratory wheezing. His abdomen is soft, nontender and nondistended. He has palpable splenomegaly with the lower spleen edge palpated 2-3 finger-breadths below the left costal margin. He has wam skin without edema or rash.

Article by Anand Selvam, MD

References:

World Malaria Report. 2015

White NJ, Pukrittayakamee S, Hien TT, et al. Malaria. The Lancet 2014; 723-735.

Agarwal A, McMorrow M, Onyango P, et al. A randomized trial of artemether-lumefantrine and dihydroartemisinin-piperaquine in the treatment of uncomplicated malaria among children in western Kenya. Malaria Journal 2013; 12:254.

Rosenthal PJ. Artesunate for the Treatment of Severe Falciparum Malaria. N Engl J Med. 2008; 388:1829-36.

Breman, JG. Conquering Malaria. Improving Population Health Workshop. Fogarty International Center. Cuernavaca, Mexico. 2003. Trampuz A, Jereb M, Muzlovic I, et al. Clinical Review: Severe Malaria. Critical Care. 2003, 7:315-323.

+ Tuberculosis

Clinical Presentation:

Latent TB: Latent TB is diagnosed with positive Tuberculin skin tests or newer ELISA tests, with negative symptoms and negative CXR Pulmonary Tuberculosis: Active pulmonary disease is characterized by 3 weeks of cough, chest pain, productive sputum or hemoptysis as well as weakness, weight loss, fevers and night sweats

Extra-Pulmonary Tuberculosis:

Lymphadenitis - the most common form of extra pulmonary tuberculosis. Cervical adenopathy is most common, but inguinal, axillary, mesenteric can occur

Skeletal - bone and joint tuberculosis = 35% of extrapulmonary TB. Tuberous arthritis is commonly in knees and hips, involving one joint, while spine (Pot’s disease), present as back pain, progressing to paralysis in ½ patients

Central nervous system - includes tuberculous meningitis (the most common presentation), intracranial tuberculomas and spinal tuberculous arachnoiditis. Present with headache for 2-3 weeks, AMS, fever and with focal CNS findings dependent on location

Abdominal tuberculosis - may involve the gastrointestinal tract, peritoneum, mesenteric lymph nodes. Present with peritonitis, perforated bowel, abdominal pain, and diarrhea Miliary TB - progressive, disseminated form of tuberculosis, that can presents as septic shock, acute respiratory distress syndrome, and multiorgan failure. Classically, CXR can reveal numerous nodules scattered throughout the lung in > 85 percent of patients

THE STATE OF TB IN THE WORLD

According to data from 2012, an estimated 27 % of all tuberculosis infected patients live in sub-Saharan Africa, with the highest prevalence being in South Africa, Botswana, Swaziland, Zimbabwe and Mozambique. The high prevalence correlates directly with HIV prevalent areas. The majority of TB is not active TB, but latent TB, when a patient is infected with M tb, but does not have symptoms and is not able to infect other individuals. ~10% of latent TB will progress to active TB

Diagnosis

Active TB is a diagnosis starting with clinical suspicion of physical exam or imaging. The gold stand confirmatory test of AFB stain/culture of sputum, tissue or fluid from site of infection is available but delayed, and if suspicion of pulmonary infection is considered, isolation measure need to be ensured. Quantiferon gold is a serum test with increased specificity. When treating in developing countries, We do not have testing, so our diagnosis will be based mainly on symptoms and risk factors, as well as history, with high index of suspicion and referral

Treatment Active TB

Preferred Regimen

Initial Phase - Daily rifampin, isoniazid, pyrazinimide, ethambutol for 8 weeks Continuation Phase - Daily rifampin, isoniazid for 18 weeks or twice weekly rifampin, isoniazid for 18 weeks Alternate Regimen

Initial Phase - Daily rifampin, isoniazid, pyrazinimide, ethambutol for 2 weeks, then twice weekly for 6 weeks Continuation Phase - Twice weekly rifampin, isoniazid for 18 weeks Latent TB

Isoniazid for 6-9 months Isoniazid, Rifapentine for 3 months Rifampin for 4 months

Written by Bret Betz, MD

+ Schistosomiasis

Background

Schistosomiasis, also known as Bilharzia or Katayama fever, is a parasitic infection caused by the parasite schistosoma. There are five species of schistosoma that can infect humans and these species are endemic in tropical and subtropical areas. Africa bears the largest disease burden and children under 14 years old are most commonly affected. Freshwater snails are the intermediate host of the parasite. Exposure to contaminated fresh water is necessary for infection. Control of the schistosomiasis disease burden is often focused around control and removal of the freshwater snail intermediate species.

Geographic distribution

S. mansoni and S. haematobium are found in Africa. S. haematobium is the only species found in the Middle East. S. japonicum is endemic in Indonesia, China, and Southeast Asia. S. mekongi is found in Cambodia and Laos, and S. intercalatum, can be found in Central and West Africa.

Stages of infection

Immediate - occurs hours to days after infection and is characterized by a maculopapular rash that is caused by parasite penetration through the skin. This infection is similar to swimmer’s itch, which occurs when non-human infecting species of Schistosomiasis penetrate the skin.

Acute - occurs days to month after infection. Symptoms are fever, headache, generalized myalgias, bloody diarrhea, RUQ pain, and/or respiratory symptoms. On physical exam patients have tender hepatomegaly and splenomegaly. CBC often shows eosinophilia. CXR can show evidence of interstitial pneumonitis.

Chronic - occurs months to years after initial infection and is caused by a granulomatous reaction to schistosoma eggs.

GI/Liver - patients can develop ulceration or microabscess of the bowel and periportal fibrosis in the liver. Symptoms include alternating diarrhea and constipation, fecal occult blood, hepatomegaly and splenomegaly.

GU - specifically from infection by S. haematobium. Symptoms include dysuria and hematuria.

CNS - mechanism of egg deposition is unknown. Symptoms include seizures and transverse myelitis.

Diagnosis

Gold standard is examination of the urine or stool for evidence of eggs. Serology testing can be used however it does not distinguish between a current and past infection.

Treatment

Praziquantal, an antihelmithic medication, which acts by killing adult worms, is the treatment of choice. Dosing is 20mg/kg x2 doses given four hours apart. If infection occurs in Southeast Asia, current recommendations are to take 30mg/kg x2 doses given four hours apart. If there is concern that a patient is early in their infection course, you should repeat the dosing several weeks later in order to kill all adult worms.

Written by Grace Lagasse, MD

+ Typhoid

Background

Salmonella enterica is a common cause of enteric fevers in developing nations. The CDC estimates more than 20 million cases yearly worldwide with just around 5000 cases in the US ( with the majority due to travel). The bacteria lives solely in humans and is transmitted via the fecal-oral route. Children and the elderly most often experience severe symptoms and are at highest risk for serious sequelae of the illness.

Clinical Presentation

Typhoid fever, true to its name, often presents with high fevers. Between 5-21 days after inoculation, patients will develop GI symptoms and fevers that increase in a stepwise manner.

Interestingly, typhoid may present with diarrhea or constipation. Diarrhea is more common at approximately 70% of cases, but constipation certainly is not uncommon. Classically, the illness progresses to intestinal bleeding and may be associated with a rash and hepatosplenomegaly. One complication to consider in patients presenting with typhoid fever is intestinal perforation. Hyperplasia and necrosis at Peyer’s patches is believed to be the underlying pathology. Rates of perforation vary between 1-20% depending on the study quoted.

Prevention

Consumption of clean food and drink is obviously key. Utilizing bottled water and avoiding ice made from non-potable water are easy to follow recommendations. Ensure foods are adequately cooked and maintain good hand washing and hygiene practices.

Vaccinations are also available. There are both a live attenuated vaccine that is administered orally and a intramuscular polysaccharide vaccine. Both have been shown to be useful, although the parenteral version is more efficacious as it offers 70% protection at 1 year. Passive immunity dwindles quickly, and repeat vaccination is recommended for frequent travelers

Treatment

Antibiotic therapy has significantly decreased the mortality rate of Typhoid fever since their introduction. Resistance patterns have led to a shift toward the third generation cephalosporins, azithromycin, and fluoroquinolones as empiric therapy, although cultures are recommended as drug-resistant strains are becoming more common. Some common drug regimens:

Ciprofloxacin: 500 bid po or IV x 7-10 days Cefixime (20 mg/kg per day orally in two divided doses) for 7 to 14 days (alt: ceftriaxone 2g IV daily) Azithromycin (1 g orally once followed by 500 mg once daily for 5-7 days or 1g po daily for 5 days)

Monitoring for complications is crucial as well. Perforation is most common during the 3rd week of illness, and as previously stated, as many as 1 in 5 cases may experience this event. Prompt surgical intervention coupled with broadened antibiotics targeting gut colonizers is recommended.

Article by Tyler Winders, MD