• View in gallery

    Relative quantity (scored as 1+, 2+, 3+, or 4+) of vaginal organisms in pregnant (A) and lactating (B) Ngäbe women from western Panamá who were positive for Lactobacillus, Bacteroides/Gardnerella, Mobiluncus, trichomoniasis, yeast, and diplococcal infection. * Indicates higher severity in pregnancy or lactation.

  • View in gallery

    Relationships among infections of the vaginal tract (Nugent score for bacterial vaginosis as well as component bacteria shown in dashed boxes [Bacteroides/Gardnerella, Mobiluncus, and Lactobacillus], trichomoniasis, yeast, diplococcal), urinary tract (AB/UTI), intestine (hookworm, Trichuris, Ascaris), and skin (scabies, impetigo) in pregnant (A) and lactating (B) Ngäbe women from western Panamá. Associations based on multiple regression analysis (P < 0.05) are indicated as positive () or negative (). Associations emerging from χ2 analysis are indicated as more () or less () than expected by chance (P < 0.005).

  • 1.

    Anderson MR, Klink K, Cohrssen A, 2004. Evaluation of vaginal complaints. JAMA 291: 13681379.

  • 2.

    Ilkit M, Guzel AB, 2011. The epidemiology, pathogenesis, and diagnosis of vulvovaginal candidosis: a mycological perspective. Crit Rev Microbiol 37: 250261.

    • Search Google Scholar
    • Export Citation
  • 3.

    Schnarr J, Smaill F, 2008. Asymptomatic bacteriuria and symptomatic urinary tract infections in pregnancy. Eur J Clin Invest 38 (Suppl 2): 5057.

    • Search Google Scholar
    • Export Citation
  • 4.

    Larocque R, Casapia M, Gotuzzo E, Gyorkos TW, 2005. Relationship between intensity of soil-transmitted helminth infections and anemia during pregnancy. Am J Trop Med Hyg 73: 783789.

    • Search Google Scholar
    • Export Citation
  • 5.

    Kandan PM, Menaga V, Kumar RR, 2011. Oral health in pregnancy (guidelines to gynaecologists, general physicians and oral health care providers). J Pak Med Assoc 61: 10091014.

    • Search Google Scholar
    • Export Citation
  • 6.

    Matevosyan NR, 2011. Periodontal disease and perinatal outcomes. Arch Gynecol Obstet 283: 675686.

  • 7.

    Feldmeier H, Heukelbach J, 2009. Epidermal parasitic skin diseases: a neglected category of poverty-associated plagues. Bull World Health Organ 87: 152159.

    • Search Google Scholar
    • Export Citation
  • 8.

    Afsar FS, 2010. Skin infections in developing countries. Curr Opin Pediatr 22: 459466.

  • 9.

    Zhang D, Mi L, Yang H, 2014. Incidence and factors influencing postpartum bacterial vaginosis: a controlled study. Chin Med J (Engl) 127: 586587.

    • Search Google Scholar
    • Export Citation
  • 10.

    Adriaens LM, Alessandri R, Sporri S, Lang NP, Persson GR, 2009. Does pregnancy have an impact on the subgingival microbiota? J Periodontol 80: 7281.

    • Search Google Scholar
    • Export Citation
  • 11.

    Moodley D, Esterhuizen T, Reddy L, Moodley P, Singh B, Ngaleka L, Govender D, 2011. Incident HIV infection in pregnant and lactating women and its effect on mother-to-child transmission in South Africa. J Infect Dis 203: 12311234.

    • Search Google Scholar
    • Export Citation
  • 12.

    Selvaraj S, Paintsil E, 2013. Virologic and host risk factors for mother-to-child transmission of HIV. Curr HIV Res 11: 93101.

  • 13.

    Schleiss MR, 2006. Role of breast milk in acquisition of cytomegalovirus infection: Recent advances. Curr Opin Pediatr 18: 4852.

  • 14.

    Amir LH, Cullinane M, Garland SM, Tabrizi SN, Donath SM, Bennett CM, Cooklin AR, Fisher JR, Payne MS, 2011. The role of micro-organisms (Staphylococcus aureus and Candida albicans) in the pathogenesis of breast pain and infection in lactating women: study protocol. BMC Pregnancy Childbirth 11: 54.

    • Search Google Scholar
    • Export Citation
  • 15.

    Betzold CM, 2012. Results of microbial testing exploring the etiology of deep breast pain during lactation: a systematic review and meta-analysis of nonrandomized trials. J Midwifery Womens Health 57: 353364.

    • Search Google Scholar
    • Export Citation
  • 16.

    Elram T, Livne A, Oren A, Gross I, Shapiro M, Mankuta D, 2008. Labor as a bacteriuric event—assessment and risk factors. J Matern Fetal Neonatal Med 21: 483486.

    • Search Google Scholar
    • Export Citation
  • 17.

    Knowles S, O'Sullivan N, Meenan A, Hanniffy R, Robson M, 2014. Maternal sepsis incidence, aetiology and outcome for mother and fetus: a prospective study. BJOG 121: 17541755.

    • Search Google Scholar
    • Export Citation
  • 18.

    Muhangi L, Woodburn P, Omara M, Omoding N, Kizito D, Mpairwe H, Nabulime J, Ameke C, Morison LA, Elliott AM, 2007. Associations between mild-to-moderate anaemia in pregnancy and helminth, malaria and HIV infection in Entebbe, Uganda. Trans R Soc Trop Med Hyg 101: 899907.

    • Search Google Scholar
    • Export Citation
  • 19.

    Adegnika AA, Ramharter M, Agnandji ST, Ateba Ngoa U, Issifou S, Yazdanbahksh M, Kremsner PG, 2010. Epidemiology of parasitic co-infections during pregnancy in Lambarene, Gabon. Trop Med Int Health 15: 12041209.

    • Search Google Scholar
    • Export Citation
  • 20.

    Ivan E, Crowther NJ, Rucogoza AT, Osuwat LO, Munyazesa E, Mutimura E, Njunwa KJ, Zambezi KJ, Grobusch MP, 2012. Malaria and helminthic co-infection among HIV-positive pregnant women: prevalence and effects of antiretroviral therapy. Acta Trop 124: 179184.

    • Search Google Scholar
    • Export Citation
  • 21.

    Liabsuetrakul T, Chaikongkeit P, Korviwattanagarn S, Petrueng C, Chaiya S, Hanvattanakul C, Kongkitkul P, Sinthuuthai C, Kalong N, Ongsawang D, Ungsathapornpon S, Ameeroh A, Bavonnarongdet P, Buadung A, 2009. Epidemiology and the effect of treatment of soil-transmitted helminthiasis in pregnant women in southern Thailand. Southeast Asian J Trop Med Public Health 40: 211222.

    • Search Google Scholar
    • Export Citation
  • 22.

    Franklin TL, Monif GR, 2000. Trichomonas vaginalis and bacterial vaginosis. Coexistence in vaginal wet mount preparations from pregnant women. J Reprod Med 45: 131134.

    • Search Google Scholar
    • Export Citation
  • 23.

    Goto A, Nguyen QV, Pham NM, Kato K, Cao TP, Le TH, Hoang QK, Le TQ, Nguyen BT, Katsube M, Ishii S, Yasumura S, 2005. Prevalence of and factors associated with reproductive tract infections among pregnant women in ten communes in Nghe An province, Vietnam. J Epidemiol 15: 163172.

    • Search Google Scholar
    • Export Citation
  • 24.

    Romoren M, Sundby J, Velauthapillai M, Rahman M, Klouman E, Hjortdahl P, 2007. Chlamydia and gonorrhoea in pregnant Batswana women: time to discard the syndromic approach? BMC Infect Dis 7: 27.

    • Search Google Scholar
    • Export Citation
  • 25.

    Lello J, Knopp S, Mohammed KA, Khamis IS, Utzinger J, Viney ME, 2013. The relative contribution of co-infection to focal infection risk in children. Proc Biol Sci 280: 20122813.

    • Search Google Scholar
    • Export Citation
  • 26.

    Cauci S, Culhane JF, 2007. Modulation of vaginal immune response among pregnant women with bacterial vaginosis by Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhoeae, and yeast. Am J Obstet Gynecol 196: 133.e1133.e7.

    • Search Google Scholar
    • Export Citation
  • 27.

    Allsworth JE, Peipert JF, 2011. Severity of bacterial vaginosis and the risk of sexually transmitted infection. Am J Obstet Gynecol 205: 113.e1113.e6.

    • Search Google Scholar
    • Export Citation
  • 28.

    Balkus JE, Richardson BA, Rabe LK, Taha TE, Mgodi N, Kasaro MP, Ramjee G, Hoffman IF, Abdool Karim SS, 2014. Bacterial vaginosis and the risk of Trichomonas vaginalis acquisition among HIV-1-negative women. Sex Transm Dis 41: 123128.

    • Search Google Scholar
    • Export Citation
  • 29.

    Ezenwa VO, Jolles AE, 2011. From host immunity to pathogen invasion: the effects of helminth coinfection on the dynamics of microparasites. Integr Comp Biol 51: 540551.

    • Search Google Scholar
    • Export Citation
  • 30.

    Friberg IM, Little S, Ralli C, Lowe A, Hall A, Jackson JA, Bradley JE, 2013. Macroparasites at peripheral sites of infection are major and dynamic modifiers of systemic antimicrobial pattern recognition responses. Mol Ecol 22: 28102826.

    • Search Google Scholar
    • Export Citation
  • 31.

    Getachew M, Tafess K, Zeynudin A, Yewhalaw D, 2013. Prevalence of soil transmitted helminthiasis and malaria co-infection among pregnant women and risk factors in Gilgel Gibe Dam area, southwest Ethiopia. BMC Res Notes 6: 263.

    • Search Google Scholar
    • Export Citation
  • 32.

    Hartgers FC, Yazdanbakhsh M, 2006. Co-infection of helminths and malaria: modulation of the immune responses to malaria. Parasite Immunol 28: 497506.

    • Search Google Scholar
    • Export Citation
  • 33.

    Supali T, Verweij JJ, Wiria AE, Djuardi Y, Hamid F, Kaisar MM, Wammes LJ, van Lieshout L, Luty AJ, Sartono E, Yazdanbakhsh M, 2010. Polyparasitism and its impact on the immune system. Int J Parasitol 40: 11711176.

    • Search Google Scholar
    • Export Citation
  • 34.

    Graham AL, Cattadori IM, Lloyd-Smith JO, Ferrari MJ, Bjornstad ON, 2007. Transmission consequences of coinfection: cytokines writ large? Trends Parasitol 23: 284291.

    • Search Google Scholar
    • Export Citation
  • 35.

    Fenton A, 2013. Dances with worms: the ecological and evolutionary impacts of deworming on coinfecting pathogens. Parasitology 140: 11191132.

    • Search Google Scholar
    • Export Citation
  • 36.

    Singer M, 2013. Development, coinfection, and the syndemics of pregnancy in sub-Saharan Africa. Infect Dis Poverty 2: 26.

  • 37.

    Sistema de Naciones Unidas, Gobierno de la República de Panamá, 2009. Objetivos de desarrollo del Milenio, III Informe de Panamá, 2009, 1st Ed. Apartadó, República de Panamá: El PNUD en Panamá, 2736.

    • Search Google Scholar
    • Export Citation
  • 38.

    Kuamri A, Goswami S, Mukherjee P, 2013. Comparative study of various methods of fetal weight estimation in term pregnancy. South Asian Feder Obst Gynae 5: 2225.

    • Search Google Scholar
    • Export Citation
  • 39.

    Fescina RH, De Mucio B, Martínez G, Alemán A, Sosa C, Mainero L, Rubino M, 2011. Monitoring Fetal Growth: Self-Instruction Manual, 2nd Ed. Montevideo, Uruguay: PAHO, 1619.

    • Search Google Scholar
    • Export Citation
  • 40.

    IOM and NRC, 2009. Weight Gain during Pregnancy: Reexamining the Guidelines. Washington, DC: The National Academies Press, 868.

  • 41.

    ACOG, 2002. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. Obstet Gynecol 99: 159167.

    • Search Google Scholar
    • Export Citation
  • 42.

    Hunter JM, Arbona SI, 1995. The tooth as a marker of developing world quality of life: a field study in Guatemala. Soc Sci Med 41: 12171240.

    • Search Google Scholar
    • Export Citation
  • 43.

    Simel DL, Rennie D, 2009. The Rational Clinical Examination: Evidence-Based Clinical Diagnosis. New York, NY: McGraw Hill / JAMA Evidence, 774.

    • Search Google Scholar
    • Export Citation
  • 44.

    Hicks MI, Elston DM, 2009. Scabies. Dermatol Ther 22: 279292.

  • 45.

    Lazar AJF, 2007. The skin. Kumar V, Abbas AK, Fausto N, Mitchell R, eds. Robbins Basic Pathology, 8th Ed. Philadelphia, PA: Elsevier Health Sciences, 843844.

    • Search Google Scholar
    • Export Citation
  • 46.

    Ollendorff AT, 2012. Cervicitis Clinical Presentation. Medscape. Available at: http://emedicine.medscape.com/article/253402-clinical-a0256. Accessed June 12, 2014.

    • Search Google Scholar
    • Export Citation
  • 47.

    Ryan CA, Courtois BN, Hawes SE, Stevens CE, Eschenbach DA, Holmes KK, 1998. Risk assessment, symptoms, and signs as predictors of vulvovaginal and cervical infections in an urban US STD clinic: implications for use of STD algorithms. Sex Transm Infect 74 (Suppl 1): S59S76.

    • Search Google Scholar
    • Export Citation
  • 48.

    Hainer BL, Gibson MV, 2011. Vaginitis. Am Fam Physician 83: 807815.

  • 49.

    Patil MJ, Nagamoti JM, Metgud SC, 2012. Diagnosis of Trichomonas vaginalis from vaginal specimens by wet mount microscopy, in pouch TV culture system, and PCR. J Glob Infect Dis 4: 2225.

    • Search Google Scholar
    • Export Citation
  • 50.

    Nugent RP, Krohn MA, Hillier SL, 1991. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J Clin Microbiol 29: 297301.

    • Search Google Scholar
    • Export Citation
  • 51.

    Coppolillo EF, Perazzi BE, Famiglietti AM, Cora Eliseht MG, Vay CA, Barata AD, 2003. Diagnosis of bacterial vaginosis during pregnancy. J Low Genit Tract Dis 7: 117121.

    • Search Google Scholar
    • Export Citation
  • 52.

    Deville WL, Yzermans JC, van Duijn NP, Bezemer PD, van der Windt DA, Bouter LM, 2004. The urine dipstick test useful to rule out infections. A meta-analysis of the accuracy. BMC Urol 4: 4.

    • Search Google Scholar
    • Export Citation
  • 53.

    Simerville JA, Maxted WC, Pahira JJ, 2005. Urinalysis: a comprehensive review. Am Fam Physician 71: 11531162.

  • 54.

    Caron F, 2010. Diagnosis and treatment of community-acquired urinary tract infections in adults: what has changed. Comments on the 2008 guidelines of the French health products safety agency (AFSSAPS). Presse Med 39: 4248.

    • Search Google Scholar
    • Export Citation
  • 55.

    WHO, 1991. Basic Laboratory Methods in Medical Parasitology, 1st Ed. England, United Kingdom: World Health Organization, 2528.

  • 56.

    Cringoli G, Rinaldi L, Maurelli MP, Utzinger J, 2010. FLOTAC: new multivalent techniques for qualitative and quantitative copromicroscopic diagnosis of parasites in animals and humans. Nat Protoc 5: 503515.

    • Search Google Scholar
    • Export Citation
  • 57.

    Knopp S, Speich B, Hattendorf J, Rinaldi L, Mohammed KA, Khamis IS, Mohammed AS, Albonico M, Rollinson D, Marti H, Cringoli G, Utzinger J, 2011. Diagnostic accuracy of Kato-Katz and FLOTAC for assessing anthelmintic drug efficacy. PLoS Negl Trop Dis 5: e1036.

    • Search Google Scholar
    • Export Citation
  • 58.

    Hellard E, Pontier D, Sauvage F, Poulet H, Fouchet D, 2012. True versus false parasite interactions: a robust method to take risk factors into account and its application to feline viruses. PLoS ONE 7: e29618.

    • Search Google Scholar
    • Export Citation
  • 59.

    Soong D, Einarson A, 2009. Vaginal yeast infections during pregnancy. Can Fam Physician 55: 255256.

  • 60.

    Edwards JL, 2010. Neisseria gonorrhoeae survival during primary human cervical epithelial cell infection requires nitric oxide and is augmented by progesterone. Infect Immun 78: 12021213.

    • Search Google Scholar
    • Export Citation
  • 61.

    Chandiramani M, Lee Y, Kindinger L, Arulkumaran S, Marchesi J, Holmes E, Nicholson J, Teoh T, MacIntyre D, Bennett P, 2014. The evolution of the vaginal microbiome throughout uncomplicated pregnancy in a UK population. Arch Dis Child Fetal Neonatal Ed 99 (Suppl 1): A12A13.

    • Search Google Scholar
    • Export Citation
  • 62.

    Yang XL, Yang HX, Duan T, He J, Sun LZ, Yu YH, Liu XH, Li XM, 2009. Vaginal microflora and relevant factors in puerperium. Zhonghua Fu Chan Ke Za Zhi 44: 496499.

    • Search Google Scholar
    • Export Citation
  • 63.

    Demirezen S, Korkmaz E, Beksac MS, 2005. Association between trichomoniasis and bacterial vaginosis: examination of 600 cervicovaginal smears. Cent Eur J Public Health 13: 9698.

    • Search Google Scholar
    • Export Citation
  • 64.

    Heller DS, Maslyak S, Skurnick J, 2006. Is the presence of Trichomonas on a Pap smear associated with an increased incidence of bacterial vaginosis? J Low Genit Tract Dis 10: 137139.

    • Search Google Scholar
    • Export Citation
  • 65.

    Uma S, Balakrishnan P, Murugavel KG, Srikrishnan AK, Kumarasamy N, Anand S, Cecelia JA, Celentano D, Mayer KH, Thyagarajan SP, Solomon S, 2006. Bacterial vaginosis in women of low socioeconomic status living in slum areas in Chennai, India. Sex Health 3: 297298.

    • Search Google Scholar
    • Export Citation
  • 66.

    Brotman RM, Klebanoff MA, Nansel TR, Yu KF, Andrews WW, Zhang J, Schwebke JR, 2010. Bacterial vaginosis assessed by gram stain and diminished colonization resistance to incident gonococcal, chlamydial, and trichomonal genital infection. J Infect Dis 202: 19071915.

    • Search Google Scholar
    • Export Citation
  • 67.

    Amdekar S, Singh V, Singh DD, 2011. Probiotic therapy: immunomodulating approach toward urinary tract infection. Curr Microbiol 63: 484490.

  • 68.

    Cadieux PA, Burton J, Devillard E, Reid G, 2009. Lactobacillus by-products inhibit the growth and virulence of uropathogenic Escherichia coli. J Physiol Pharmacol 60 (Suppl 6): 1318.

    • Search Google Scholar
    • Export Citation
  • 69.

    Liu MB, Xu SR, He Y, Deng GH, Sheng HF, Huang XM, Ouyang CY, Zhou HW, 2013. Diverse vaginal microbiomes in reproductive-age women with vulvovaginal candidiasis. PLoS ONE 8: e79812.

    • Search Google Scholar
    • Export Citation
  • 70.

    Dea-Ayuela MA, Rama-Iniguez S, Bolas-Fernandez F, 2008. Enhanced susceptibility to Trichuris muris infection of B10Br mice treated with the probiotic Lactobacillus casei. Int Immunopharmacol 8: 2835.

    • Search Google Scholar
    • Export Citation
  • 71.

    McClemens J, Kim JJ, Wang H, Mao YK, Collins M, Kunze W, Bienenstock J, Forsythe P, Khan WI, 2013. Lactobacillus rhamnosus ingestion promotes innate host defense in an enteric parasitic infection. Clin Vaccine Immunol 20: 818826.

    • Search Google Scholar
    • Export Citation
  • 72.

    Yatich NJ, Funkhouser E, Ehiri JE, Agbenyega T, Stiles JK, Rayner JC, Turpin A, Ellis WO, Jiang Y, Williams JH, Afriyie-Gwayu E, Phillips T, Jolly PE, 2010. Malaria, intestinal helminths and other risk factors for stillbirth in Ghana. Infect Dis Obstet Gynecol 2010: 350763.

    • Search Google Scholar
    • Export Citation
  • 73.

    Nguyen PH, Nguyen KC, Nguyen TD, Le MB, Bern C, Flores R, Martorell R, 2006. Intestinal helminth infections among reproductive age women in Vietnam: prevalence, co-infection and risk factors. Southeast Asian J Trop Med Public Health 37: 865874.

    • Search Google Scholar
    • Export Citation
  • 74.

    Fleming FM, Brooker S, Geiger SM, Caldas IR, Correa-Oliveira R, Hotez PJ, Bethony JM, 2006. Synergistic associations between hookworm and other helminth species in a rural community in Brazil. Trop Med Int Health 11: 5664.

    • Search Google Scholar
    • Export Citation
  • 75.

    Bethony J, Brooker S, Albonico M, Geiger SM, Loukas A, Diemert D, Hotez PJ, 2006. Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm. Lancet 367: 15211532.

    • Search Google Scholar
    • Export Citation
  • 76.

    Scott ME, 2008. Ascaris lumbricoides: a review of its epidemiology and relationship to other infections. Ann Nestlé 66: 1127.

  • 77.

    Halpenny CM, Paller C, Koski KG, Valdes VE, Scott ME, 2013. Regional, household and individual factors that influence soil transmitted helminth reinfection dynamics in preschool children from rural indigenous Panama. PLoS Negl Trop Dis 7: e2070.

    • Search Google Scholar
    • Export Citation
  • 78.

    Tarafder MR, Carabin H, McGarvey ST, Joseph L, Balolong E Jr, Olveda R, 2011. Assessing the impact of misclassification error on an epidemiological association between two helminthic infections. PLoS Negl Trop Dis 5: e995.

    • Search Google Scholar
    • Export Citation
  • 79.

    Fenton A, Viney ME, Lello J, 2010. Detecting interspecific macroparasite interactions from ecological data: patterns and process. Ecol Lett 13: 606615.

    • Search Google Scholar
    • Export Citation
  • 80.

    Myziuk L, Romanowski B, Brown M, 2001. Endocervical gram stain smears and their usefulness in the diagnosis of Chlamydia trachomatis. Sex Transm Infect 77: 103106.

    • Search Google Scholar
    • Export Citation
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 

 

 

Interactions Among Urogenital, Intestinal, Skin, and Oral Infections in Pregnant and Lactating Panamanian Ngäbe Women: A Neglected Public Health Challenge

View More View Less
  • Institute of Parasitology and Centre for Host-Parasite Interactions, McGill University, Ste-Anne de Bellevue, Quebec, Canada; School of Dietetics and Human Nutrition, McGill University, Ste-Anne de Bellevue, Quebec, Canada; Department of Biochemistry, University of Panamá, Panamá City, Panamá; Department of Nutritional Health, Ministry of Health, Panamá City, Panamá

Interrelationships among bacteria, protozoa, helminths, and ectoparasites were explored in a cross-sectional survey of 213 pregnant and 99 lactating indigenous women. Prevalences in pregnancy and lactation, respectively, were: vaginitis (89.2%; 46.8%), vaginal trichomoniasis (75.3%; 91.1%), bacterial vaginosis (BV; 60.6%; 63.3%), hookworm (56.6%; 47.8%), asymptomatic bacteriuria/urinary tract infection (AB/UTI; 56.2%; 36.2%), cervicitis (33.3%; 6.3%), vaginal yeast (24.9%; 11.4%), Ascaris (32.5%; 17.4%), vaginal diplococci (20.4%; 31.6%), caries (19.7%; 18.2%), scabies (17.4%; 8.1%), and Trichuris (12.5%; 8.7%). Multiple regressions revealed positive associations during pregnancy (trichomoniasis and AB/UTI; diplococci and Ascaris) and lactation (yeast and scabies). Negative associations were detected in pregnancy (BV and trichomoniasis; hookworm and diplococci) and lactation (BV and yeast). Vaginal Lactobacillus reduced odds of diplococci in pregnancy and lactation, but increased Ascaris eggs per gram (epg) and odds of trichomoniasis in pregnancy and yeast in lactation. These associations raised a concern that treatment of one condition may increase the risk of another.

Introduction

In remote, extremely impoverished communities in developing countries, there is little scientific information on the range of infections during pregnancy and lactation. In addition to malaria, toxoplasmosis, tuberculosis, human immunodeficiency virus (HIV), and other viral infections, pregnant women may be infected with a wide variety of bacterial, fungal, and parasitic infections including bacterial vaginosis (BV), vaginal candidiasis, trichomoniasis,1,2 asymptomatic bacteriuria/urinary tract infections (AB/UTI) most often caused by Escherichia coli,3 intestinal nematode infections (Trichuris, Ascaris, and hookworm),4 dental and periodontal disease,5,6 and skin infections (scabies, bacterial and fungal infections), which are common under conditions of poor hygiene, poor nutritional status, and overcrowding.7,8

Compared with pregnancy, BV is reportedly more prevalent during lactation,9 whereas periodontal disease (but not periodontitis) and associated microflora are less common in lactating women.10 Information on other infections during lactation is largely limited to those transmitted during breast-feeding such as HIV11,12 and cytomegalovirus,13 mammary infections produced by Staphylococcus spp. and Candida spp.,14,15 UTI associated with institutional vaginal delivery,16 and puerperal sepsis mostly associated with vaginal infections.17

In conditions of poverty where access to health care is limited, coinfection is likely common. Yet research on coinfections during pregnancy and lactation has primarily focused on the associations of HIV and malaria with other pathogens including intestinal nematodes1820 or associations with other infections of the intestine21 or the reproductive tract.2224 For example, intestinal nematode infections are often positively associated with one another25 and BV is often positively associated with other common vaginal pathogens.2628 Much less is understood about interactions among vaginal, intestinal, urinary tract, skin, and oral infections. Nematode parasites have been reported to influence the progression of microparasite infections.29,30 For example, pregnant women infected with Ascaris had increased risk of malaria in both Gabon19 and Ethiopia,31 but those with higher intensity of Ascaris had reduced risk of malaria perhaps as a result of the strong anti-inflammatory response induced by Ascaris.32,33 Given that host defense mechanisms (both innate and adaptive) are increasingly understood to be sensitive to the presence of coexisting pathogens through the systemic response that they elicit,3336 the impact of one infection is likely to extend to other regions of the body.

The objectives of this observational cross-sectional survey were 1) to characterize the range of infections (oral, skin, respiratory, urinary, vaginal, and intestinal) during pregnancy and the first 6 months of lactation in Ngäbe women using a clinical exam and locally available laboratory tests; 2) to determine whether prevalence of infections differed among trimesters or between pregnancy and lactation; 3) to explore associations between the presence or severity of one pathogen and the community of other pathogens; and 4) to determine whether such associations were similar in pregnant and lactating women. The study was conducted in a remote, rural region of western Panamá within the Comarca, an administrative area inhabited by the Ngäbe-Buglé, the largest indigenous population of Panamá, and comprising a territory between Bocas del Toro, Chiriquí, and Veraguas Provinces where over 60% of households live in extreme poverty.37 Routine prenatal care is limited to basic clinical measurements (vital signs, fundal height, fetal cardiac rate, fetal movements, and presence of edema) performed by an auxiliary nurse at the local health center. Depending on the distance from the nearest hospital, a physician may provide more detailed pregnancy follow-up from once a week to a few times a year. Most deliveries occur at home and are attended by traditional midwives or relatives.

Materials and Methods

Ethical considerations.

Ethical approval was obtained from McGill University in Canada, the Gorgas Memorial Institute Ethics Board in Panamá, the Panamanian Ministry of Health, provincial and local health authorities, and indigenous authorities. All mothers were informed of their right to refuse to participate and to withdraw at any time. Participants signed a consent form. Those who were not able to write marked the consent form with their fingerprint, in the presence of a witness who signed the consent form. Participants received no direct financial compensation but they received a complete medical evaluation and verbal referral when follow-up was needed.

Study design.

An observational cross-sectional survey was conducted with indigenous Ngäbe pregnant women and lactating women with infants < 6 months old. For the sample of pregnant women, the three inclusion criteria were 1) pregnancy as detected either by a positive pregnancy test for women with amenorrhea > 5 weeks or a physical exam by staff at the health centers, community health workers, or traditional midwives; 2) homes within a 2-hour walk of one of the 14 health centers; and 3) mothers well enough to walk to the health centers. The only exclusion criteria were twin pregnancy or abnormal pregnancy (ectopic pregnancy or hydatidiform mole). Of the 217 pregnant women approached between August and October 2010, 214 agreed to participate. One participant was excluded because of abnormal pregnancy (hydatidiform mole), resulting in a participant population of 213. No cases of ectopic pregnancy were found.

For the sample of lactating women, the three inclusion criteria were 1) women who had a singleton delivery within the last 6 months and whose babies were living with them; 2) homes within a 2-hour walk of one of the 14 health centers; and 3) mothers well enough to walk to the health centers. Of the 99 women approached, all agreed to participate. Only one woman recruited in the sample of lactating women had also been recruited into the pregnancy sample.

A clinical exam was used to diagnose skin (scabies, impetigo, and dermatomycosis), oral (caries, gingivitis), respiratory (cold, bronchitis), and vaginal tract (vaginitis, cervicitis) infections. Laboratory examinations of urine and stool samples and vaginal smears were used to diagnose AB/UTI, BV including Bacteroides/Gardnerella, Mobiluncus and Lactobacillus, vaginal trichomoniasis, vaginal diplococcal infection, vaginal yeast infection, intestinal parasites (Ascaris, Trichuris, hookworm, Giardia, and Entamoeba coli). Comparisons were made among trimesters and between pregnancy and lactation and associations among organisms were explored.

Participant recruitment.

We identified 14 health centers located in the districts of Besikó (Soloy, Emplanada de Chorcha and Quebrada de Hacha), Nole Duima (Hato Chamí, Oma, Lajero and Quebrada Guabo), Müna (Alto Caballero and Chichica), and Mironó (Hato July, Kuerima, Hato Pilón, Quebrada de Loro and Hato Corotú) with year-round road access to the regional hospital in San Felix. Meetings were held at the health centers with all staff and associated community health workers and traditional midwives to explain the study and to provide training on pregnancy follow-up and recognition of complicated pregnancies. The staff, community health workers, and midwives then contacted all pregnant women and lactating mothers with infants up to 6 months old within their respective catchment areas, explained the research project and invited them to attend an information session at the local health center where objectives, procedures, and confidentiality were explained and fully informed consent was obtained. Pregnant women staying at the temporary home near the San Felix hospital were also invited to participate. We estimated that about 90% of eligible women in the catchment area met with the research team during our visit to their local health center.

Medical history, clinical exam, and health questionnaire.

All women were seen at their local health center or at the temporary home where they received a complete clinical evaluation. This included a questionnaire on obstetric history (age, parity, and gestational age [GA] calculated according to reported date of last menstrual period) and a questionnaire on symptoms of infection. The physical examination included anthropometry (measured with SECA® balances [SECA Deutschland, Hamburg, Germany] with height rod, available at the health centers) and blood pressure (BP), measured with an Omron HEM-790IT® automatic BP monitor (OMRON Healthcare Europe B.V., Hoofddorp, The Netherlands) while seated and after a minimum 15 minutes resting period. Body mass index (BMI) measurements for pregnant women were calculated ([maternal − fetal weight in kilograms]/[maternal height in meter]2) where fetal weight was estimated using Johnson's formula (fetal weight [g] = symphysis fundal height [cm] − 13 × 155),38 and women were classified as underweight, normal, or overweight for GA compared against Pan American Health Organization (PAHO) standards for GA.39 BMI for lactating women was classified as for the general population: underweight (BMI < 19.8 kg/m2), normal (19.8–26.0 kg/m2), overweight (26.1–29.0 kg/m2), or obese (> 29 kg/m2).40 Presence of hypertension was defined as blood pressure > 140/90.41

A medical exam conducted by a physician was used to diagnose oral, respiratory, skin, and vaginal infections. Oral infections were detected through direct visual exam for presence or absence of dental cavities (caries) or inflammation of the gum (gingivitis).42 Symptoms of mild upper respiratory tract infection (sneezing, runny or stuffy nose, sore throat), lower respiratory tract symptoms (cough associated with auscultator findings such as bronchial rales or crepitus),43 and complicated upper UTI (fever, costovertebral angle tenderness, flank pain, nausea, or vomiting)3 were recorded as present or absent. Among skin infections, lesions typical of scabies (small erythematous symmetrical papulovesicular rash),44 superficial dermatomycosis (pruritic erythematous macules with superficial scales), and impetigo (confluent macules with honey-colored crust)45 were recorded as present or absent. A small part of the room in the health center was temporarily screened off for the genital exam. After an explanation about the genital exam, women were asked to lie in the gynecological position and a disposable speculum was placed into the vagina. Direct visual exam allowed the clinical diagnosis of vaginitis based on vaginal discharge and/or irritation of the vaginal wall, and of cervicitis based on erythematous, edematous, or easily friable appearance.46 Both vaginitis and cervicitis severity were graded as mild, moderate, or severe depending on the intensity and extent of the symptoms.47,48

Vaginal smears.

During the genital examination, a sterile swab was used to take a sample of vaginal secretion or discharge from all participants. The swab was placed in a tube with 1 mL sterile saline solution, immediately refrigerated and kept on ice during transport to the laboratory. Direct microscopic examination of wet mounts was done by an experienced laboratory technician for mobile forms of Trichomonas vaginalis (sensitivity of 60%)49 and budding yeast cells and/or hyphae of vaginal yeast infection (sensitivity 65–85%).48 Severity of vaginal yeast was scored according to the number per high-power field (hpf) as 0 (absent), 1+ (1/hpf), 2+ (2/hpf), 3+ (3/hpf), or 4+ (4 or more/hpf).

Vaginal smears were gram-stained to detect bacterial and protozoan pathogens. Quantity of Lactobacillus spp. and severity of Bacteroides spp./Gardnerella spp. and Mobiluncus spp. were scored as 0 (absent), 1+ (1–5/hpf), 2+ (6–10/hpf), 3+ (11–20/hpf), and 4+ (> 20/hpf) by an experienced laboratory technician and confirmed by a trained clinician. Diagnosis of BV was based on the Nugent score, calculated according to the methods described by Nugent and others50: Bacteroides/Gardnerella score + (4 − Lactobacillus score) + (Mobiluncus score/2). A Nugent score of 0–3 reflected normal vaginal microflora, 4–6 corresponded to intermediate vaginal microflora, and 7–10 was diagnostic for BV, with a sensitivity of 97%.51 Severity of Trichomonas was scored, according to the number of organisms/hpf on the gram stain, as 0 (absent), 1+ (1/hpf), 2+ (2/hpf), 3+ (3/hpf), or 4+ (4 or more/hpf). Results from the gram-stained slides for trichomoniasis were used for statistical analysis given the higher estimates of prevalence detected in the gram stain compared with our wet mounts. Given the technical difficulty in distinguishing extracellular diplococci from similar pathologic bacteria, presence and severity of diplococcal infection was scored according to the number of leukocytes/hpf that contained diplococci as 0 (absent), 1+ (1/hpf), 2+ (2/hpf), 3+ (3/hpf), or 4+ (4 or more/hpf). No culture or molecular diagnostic techniques were available in this research setting.

As part of the routine assessment of pregnant women in the San Felix Hospital coverage area, results from the Venereal Disease Research Laboratory (VDRL) test (indicator of syphilis) using the unheated serum reagin antibody test from Wiener® laboratories (Rosario, Argentina) were also available for 172 pregnant participants. Also, the provincial HIV program manages an active screening of pregnant women across the Comarca using Advanced Quality Rapid Anti-HIV (1&2) test (InTec PRODUCTS, INC., Xiamen, China), a rapid immunochromatographic assay for the qualitative detection of antibodies to HIV in whole blood, serum, or plasma.

Urine samples.

Urine samples were analyzed by an experienced laboratory technician using dipstick URISCAN® strips (YD Diagnostics, Kyunggi-Do, Korea) on a Miditron-M semiautomated reflectance photometer (Roche Diagnostics GmbH, Mannheim, Germany) with reagents for semiquantitative measurement of UTI (leukocyte esterase, nitrites, hemoglobin [Hb], and urinary pH), proteinuria as an indicator of renal pathology or preeclampsia, and glucose as an indicator of gestational diabetes. In addition, fresh urine was centrifuged at 3,000 rpm for 5 minutes, the supernatant was decanted and the sediment resuspended in the remaining liquid. A drop of the sediment was examined using low- and high-power magnification from which leukocytes, bacteria, and red blood cells were recorded and their co-occurrence with mucus and epithelial cells were noted as controls for vaginal contamination. Presence of AB/UTI was diagnosed based on bacteria ≥ 1+/hpf in microscopic examination of urine (sensitivity of 46–58%, specificity of 89–94%) combined with either leukocytes ≥ 5/hpf (sensitivity alone of 90–96%, specificity of 47–50%) or red blood cells ≥ 5/hpf (sensitivity alone of 18–44%, specificity of 88–89%), or URISCAN results with leukocyte esterase ≥ 2+ on a scale of 0–3+ (sensitivity alone of 72–97%, specificity 41–86%), presence of nitrites (sensitivity alone 19–48%, specificity 92–100%), or Hb ≥ 1+ on a scale of 0–4+ (sensitivity of 68–92%, specificity of 42–46%).52,53 AB/UTI was ruled out in samples when high amounts of mucus and/or epithelial cells were observed under the microscope. Urine culture was not possible at the study location. Complicated UTI was ruled out based on absence of symptoms.54

Stool samples.

All stool samples were examined using a direct smear for protozoan infections by an experienced laboratory technician trained in distinguishing Entamoeba coli from Entamoeba histolytica. When a sample of sufficient volume and appropriate consistency was available, nematode intensity (eggs per gram [epg]) was recorded using Kato-Katz55 and FLOTAC56 techniques. A positive result from any of the three methods was used to calculate the prevalence of nematode infections, and FLOTAC results were used to determine the epg, given its higher sensitivity for Trichuris and hookworm when compared with Kato-Katz technique.57

Data analysis.

All data were analyzed using STATA 10 (StataCorp LP, College Station, TX). Results are presented as raw mean ± standard error of the mean (SEM) or prevalence (%). The level of significance was set at P < 0.05 unless otherwise indicated.

Prevalence of infection was compared among trimesters and between pregnancy and lactation using χ2 tests. The Kruskal–Wallis nonparametric analysis of variance was used to determine if the severity of symptoms of BV differed by trimester or between pregnant and lactating women.

Analyses of coinfections were performed first using χ2 tests to determine whether infections in pregnant women or in lactating women occurred together more or less frequently than expected by chance. In cases where expected values were < 5, the Fisher's exact test was used. Given that an average of 10 tests were conducted for each infection within pregnancy and within lactation samples, we applied the Bonferroni correction to obtain a more conservative critical P value of 0.005 but have also reported actual P values for all analyses with P < 0.05. In addition, multiple regression analyses were used to explore the interrelationships among infections, while controlling for GA in models for pregnant women or weeks after delivery in models for lactating women. Models were generated only for those infections where laboratory analyses revealed a prevalence > 10% in at least one trimester or during lactation, and where the infection was considered pathogenic. Multiple logistic regression was used to generate a model for the presence of AB/UTI. Multiple ordered logistic regression was used to generate models for the severity of BV, vaginal trichomoniasis, vaginal yeast, and vaginal diplococcal infection. Given that the Nugent score incorporates information on two sets of pathogens (Bacteroides/Gardnerella and Mobiluncus) and one competitive bacteria (Lactobacillus), models were generated using either the Nugent score for BV or the individual bacteria in an effort to better understand interrelationships among the vaginal microflora. Stepwise regression was used to generate models of Ascaris, Trichuris, and hookworm epg (square root transformed [sqrt]).

In all cases, the independent variables included in each multiple regression model are listed as a footnote to the table. The ratio of number of factors to sample size was < 0.10, indicating that logistic regression was robust to the effect of shared risk factors.58 In all models, collinearity among variables in each model was tested to confirm that the variance inflation factor (VIF) was < 2.5. Final models report only those variables that entered with a P < 0.15.

Results

Study response rate.

Data from clinical exams and vaginal wet mounts were available for all women. Cervicovaginal exams and vaginal smears were done on 211 pregnant women and 79 lactating women that did not have vaginal bleeding at the time of the exam. Urine samples were collected from 208 pregnant and 79 lactating women. Of the stool samples received (120 pregnant and 23 lactating women), Kato-Katz technique was used on 105 pregnant and 17 lactating women, and FLOTAC was used on 74 pregnant and 9 lactating women.

Characteristics of study participants.

Pregnant women.

Pregnant women were 24 ± 0.5 years old (13–44 years), 11.3% were in the first trimester, 37.6% in the second trimester, and 51.2% in the third trimester. Among the women, 29.1% were adolescents (≤ 19 year) and 13.1% were ≥ 35 year; 28.1% were primiparous and 32% were in their fifth or more pregnancy. Based on BMI corrected for GA, 9.8% were underweight and 23% were overweight. Mean systolic BP was 103 ± 11 mmHg and mean diastolic BP was 62 ± 9 mmHg; none were positive for hypertension but protein was found in 11 urine samples (trace in 5 samples, 1+ in 6 urine samples). None of the pregnant women were positive for gestational diabetes based on presence of glucosuria.

Lactating mothers.

Mothers of infants < 6 months old were 25.1 ± 0.7 years old (14–42 years). All were breast-feeding and only 15% had started giving complementary food to their babies. For 20.2% of women, this was their first child; 25.2% of mothers had five or more children. Based on BMI, 24.4% were overweight and an additional 15.1% were obese; only one woman was underweight. Mean systolic BP was 109.4 ± 1.4 mmHg and mean diastolic BP was 68.4. ± 1.1 mmHg.

Prevalence and severity of clinically identified infections.

Clinical examination revealed respiratory, skin, oral, and vaginal infections (Table 1). The prevalence of respiratory infections including both upper respiratory tract infection and bronchitis was low (6.1% in pregnancy, 5% in lactating women), as was the prevalence of dermatomycosis, impetigo, and gingivitis. Scabies was more prevalent in pregnant (17.4%) compared with lactating women (8.1%) (Table 1). Caries was equally prevalent during pregnancy (19.7%) and lactation (18.2%). Although few women complained of genital discomfort, direct visualization of the vaginal tract and cervix allowed the detection of different degrees and characteristics of vaginal discharge (thick, foaming, mucoid adherent, or chunky) or cervicitis in 92% pregnant women and 50% lactating women. Both vaginitis and cervicitis were more prevalent in pregnant compared with lactating women (Table 1) and of greater severity (data not shown). Gingivitis was only detected in the third trimester (8.2%), but prevalence of all other infections was similar among trimesters (data not shown).

Table 1

Comparison of the prevalence of clinically diagnosed infections between pregnant (N = 213) and lactating (N = 99) Ngäbe women from western Panamá*

 Prevalence (%)P > χ2
PregnancyLactation
Cold, sinusitis3.73.0ns
Bronchitis4.02.0ns
Scabies17.48.10.030
Dermatomycosis1.83.0ns
Impetigo1.85.0ns
Caries19.718.2ns
Gingivitis4.25.0ns
Vaginitis89.246.8< 0.0001
Cervicitis33.36.3< 0.0001

ns = nonsignificant (P > 0.05).

χ2 or Fisher's exact test.

N = 79 lactating women.

Prevalence and severity of laboratory diagnosed infections.

Laboratory analyses identified a total of 12 bacteria, protozoa, and helminths (Table 2). Participants lived in a non-endemic area for malaria, and no HIV-positive women were identified.

Table 2

Comparison of the prevalence of laboratory-diagnosed infections between pregnant and lactating Ngäbe women from western Panamá*

 PregnancyLactationP > χ2
nPrevalence (%)nPrevalence (%)
AB/UTI20856.29436.20.001
Bacterial vaginosis21160.67963.3ns
Lactobacillus21153.57926.6< 0.0001
Bacteroides/Gardnerella21193.87997.5ns
Mobiluncus21182.47987.3ns
Vaginal trichomoniasis21175.37991.10.003
Vaginal yeast21324.97911.40.012
Vaginal diplococcal infection21120.47931.60.044
Ascaris lumbricoides12032.52317.4ns
Hookworm12056.62347.8ns
Trichuris trichiura12012.5238.7ns
Entamoeba coli1202.5234.3ns
Giardia spp.12010.8234.3ns

AB/UTI = asymptomatic bacteriuria/urinary tract infection; ns = nonsignificant (P > 0.05).

χ2 test or Fisher's exact test.

Diagnosed on the basis of the Nugent score.

Nonpathogenic.

Urinary tract infections.

The prevalence of AB/UTI was higher in pregnant (56.2%) than in lactating (36.2%) women (Table 2); no symptoms of complicated UTI were reported by any of the participants. AB/UTI prevalence did not differ among trimesters (data not shown).

Vaginal infections.

Among the vaginal infections, 97.2% of pregnant women and 97.4% of lactating women were positive for at least one of BV, vaginal trichomoniasis, yeast, and diplococcal infection. No differences in severity of the vaginal microflora were detected among trimesters (data not shown).

BV diagnosed using the Nugent score was of similar prevalence in pregnancy and lactation (60.6 and 63.3%, respectively) (Table 2). Commensal Lactobacillus was more common, and numbers were higher in pregnant compared with lactating women whereas severity of Mobiluncus was higher in lactating women; the severity of Bacteroides/Gardnerella did not differ between pregnant and lactating women (Table 2, Figure 1). Vaginal trichomoniasis was more prevalent in lactating women (91.1%) than in pregnant women (75.3%) and of greater severity (Figure 1). Diplococcal infection was also more prevalent during lactation (31.6% versus 20.4% during pregnancy), but severity was higher among pregnant women (Figure 1). On the other hand, vaginal yeast infection was more frequent (24.9%) and more severe (Figure 1) in pregnant than in lactating women (11.4%).

Figure 1.
Figure 1.

Relative quantity (scored as 1+, 2+, 3+, or 4+) of vaginal organisms in pregnant (A) and lactating (B) Ngäbe women from western Panamá who were positive for Lactobacillus, Bacteroides/Gardnerella, Mobiluncus, trichomoniasis, yeast, and diplococcal infection. * Indicates higher severity in pregnancy or lactation.

Citation: The American Society of Tropical Medicine and Hygiene 92, 6; 10.4269/ajtmh.14-0547

Among the 92% (196) of pregnant and 50% (40) of lactating women clinically diagnosed with cervico-vaginitis, only 5 (2.6%) pregnant women and 1 (2.0%) lactating woman had no pathological microorganisms. Among those without clinical signs of vaginitis or cervicitis, all 17 pregnant women and all but one lactating woman were positive for at least one of the vaginal pathogens.

VDRL tests for syphilis were reactive in 5 (2.9%) of the 172 pregnant women tested (2 at 1:1 dilution and 1 each at 1:4, 1:8, and 1:32 dilutions). Four of the VDRL reactive women had clinical vaginitis and the fifth had dermal lesions; all mentioned partner promiscuity. Even though no confirmatory tests were available, local physicians treated these five women for syphilis.

Intestinal infections.

None of the women mentioned gastrointestinal symptoms, but laboratory analyses revealed that 67.5% pregnant and 52.2% lactating women were infected with at least one intestinal pathogen (Ascaris, Trichuris, hookworm, and Giardia) (Table 2). Prevalence of Ascaris and Trichuris did not differ among trimesters or between pregnant and lactating women (Table 2), but hookworm prevalence was higher in the second and third trimesters (58% and 62%, respectively) compared with the first trimester (18%) (P = 0.024). Giardia spp. was detected in 10.8% pregnant and 4.3% lactating women. Nonpathogenic Entamoeba coli was detected in 2.5% pregnant and 4.3% lactating women.

Concurrent infections.

Based on bivariate analyses and using a stringent cutoff of P < 0.005, several pathogens occurred together more frequently than expected based on their prevalence in the population whereas others co-occurred less than expected. During pregnancy (Table 3), the BV pathogens Bacteroides/Gardnerella and Mobiluncus co-occurred more than expected whereas Bacteroides/Gardnerella was less common in the mothers with the competitive Lactobacillus. Mothers diagnosed with BV by the Nugent score were more likely to have vaginal diplococcal infection but less likely to have vaginal trichomoniasis. Lactobacillus and diplococcal infection co-occurred less frequently than expected whereas Lactobacillus co-occurred more than expected with trichomoniasis. Finally, hookworm co-occurred with Trichuris more than expected by chance.

Table 3

Co-occurrence of infections during pregnancy and lactation in Ngäbe women from western Panamá*

 Observed % vs. Expected %P
Pregnancy
Bacteroides/Gardnerella + Mobiluncus80.1 > 77.3< 0.0001
Lactobacillus + Bacteroides/Gardnerella47.7 < 50.20.003
Lactobacillus + Mobiluncus40.7 < 44.10.009
 BV + vaginal diplococcal infection19.4 > 12.3< 0.0001
 BV + vaginal trichomoniasis39.3 < 45.6< 0.0001
Lactobacillus + vaginal diplococcal infection2.8 < 15.3< 0.0001
Lactobacillus + vaginal trichomoniasis47.4 > 40.2< 0.0001
Bacteroides/Gardnerella + vaginal trichomoniasis69.2 < 70.60.041
Mobiluncus + vaginal diplococcal infection19.4 > 16.80.012
 Hookworm + Trichuris11.7 > 7.10.002
 Hookworm + Ascaris23.3 > 18.40.020
 Hookworm + vaginal diplococcal infection6.7 < 11.40.011
Lactation
Lactobacillus + vaginal diplococcal infection0 < 8.4< 0.0001
 BV + vaginal yeast infection2.5 < 7.20.010
Lactobacillus + vaginal yeast infection7.6 > 3.00.009
 Scabies + impetigo3.0 > 0.40.003
 Gingivitis + dermatomycosis2.0 > 0.10.006
Ascaris + vaginal diplococcal infection18.7 > 4.30.007

BV = bacterial vaginosis.

Significance set at P < 0.005 based on Bonferroni correction for multiple comparisons.

During lactation (Table 3), Lactobacillus co-occurred with diplococcal infection less than expected, whereas scabies and impetigo co-occurred more frequently than expected.

Presence of AB/UTI.

The odds of AB/UTI were higher in mothers with more severe vaginal trichomoniasis (odds ratio [OR] = 1.33, 95% confidence interval [CI] = 1.03–1.80) and with more severe BV based on the Nugent score (OR = 2.03, 95% CI = 1.01–3.74) (model not shown). When the Nugent score was replaced with data on individual bacteria (Table 4), the likelihood of AB/UTI was also higher in mothers with more severe vaginal trichomoniasis (OR = 1.38, 95% CI = 1.04–1.84), and the quantity of commensal lactobacilli was negatively associated with AB/UTI (OR = 0.78, 95% CI = 0.63–0.95). During lactation (Table 4), the odds of AB/UTI were higher in women with higher severity of Mobiluncus (OR = 1.72, 95% CI = 1.05–2.81).

Table 4

Final multiple logistic regression model for AB/UTI in pregnant and lactating Ngäbe women from western Panamá*

 OR ± SE95% CIP
Pregnancy
 Vaginal trichomoniasis, severity1.38 ± 0.201.04, 1.840.025
Lactobacillus, quantity§0.78 ± 0.080.63, 0.950.017
Lactation
Mobiluncus, severity§1.72 ± 0.431.05, 2.810.029

AB/UTI = asymptomatic bacteriuria/urinary tract infection; CI = confidence interval; hpf = high-power field; SE = standard error; OR = odds ratio; VIF = variance inflation factor.

AB/UTI coded as 0 = absent; 1 = present.

Variables entered in model: gestational age; presence of caries and scabies; quantity of Lactobacillus; severity of Bacteroides/Gardnerella, Mobiluncus, vaginal trichomoniasis, yeast, and diplococcal infection. Overall model P = 0.017; N = 207; VIF = 1.92.

Coded as 0 = absent; 1+ = 1/hpf; 2+ = 2/hpf; 3+ = 3/hpf; 4+ = 4 or more/hpf.

Coded as 0 = absent; 1+ = 1–5/hpf; 2+ = 6–10/hpf; 3+ = 11–20/hpf; 4+ = > 20/hpf.

Variables entered in model: weeks after delivery; presence of caries and scabies; quantity of Lactobacillus; severity of Bacteroides/Gardnerella, Mobiluncus, vaginal trichomoniasis, yeast, and diplococcal infection. Overall model: P = 0.022; N = 74; VIF = 1.00.

Severity of BV.

Among pregnant women, the odds of more severe BV were lower in pregnant women with more severe vaginal trichomoniasis (OR = 0.54, 95% CI = 0.44–0.68), but higher in mothers with more severe diplococcal infection (OR = 1.80, 95% CI = 1.43–2.25) (Table 5). During lactation (Table 6), the odds of more severe BV were lower in mothers with more severe vaginal yeast infection (OR = 0.30, 95% CI = 0.10–0.87).

Table 5

Multiple ordered logistic regression models for severity of laboratory-diagnosed cervicovaginal infections in 207 pregnant Ngäbe women from western Panamá

 OR ± SE95% CIP
Bacterial vaginosis severity*
 Vaginal trichomoniasis, severity0.54 ± 0.060.44, 0.68< 0.0001
 Vaginal diplococcal infection, severity1.80 ± 0.211.43, 2.25< 0.0001
 Vaginal yeast infection, severity1.31 ± 0.220.94, 1.830.110
Vaginal trichomoniasis severity§
 Vaginal diplococcal infection, severity1.33 ± 0.741.02, 1.720.030
Lactobacillus, quantity1.97 ± 0.211.60, 2.42< 0.0001
Mobiluncus, severity1.23 ± 0.140.95, 1.580.110
Vaginal yeast infection severity**
 GA, week0.97 ± 0.010.94, 1.000.122
 Vaginal diplococcal infection, severity1.36 ± 0.191.02, 1.800.032
Bacteroides/Gardnerella, severity1.79 ± 0.481.05, 3.050.032
Lactobacillus, quantity1.48 ± 0.310.98, 2.250.064
Vaginal diplococcal infection severity††
 GA, week1.03 ± 0.020.99, 1.070.105
Lactobacillus, quantity0.26 ± 0.080.14, 0.47< 0.0001
 Vaginal yeast infection, severity1.46 ± 0.330.93, 2.300.098
 Vaginal trichomoniasis, severity1.30 ± 0.210.94, 1.810.114

CI = confidence interval; GA = gestational age; hpf = high-power field; OR = odds ratio; SE = standard error; VIF = variance inflation factor.

Bacterial vaginosis severity according to Nugent score.

Variables entered in model: GA; presence of caries and scabies; severity of vaginal trichomoniasis, yeast, and diplococcal infection. Overall model: P < 0.001; VIF = 1.00.

Coded as 0 = absent; 1+ = 1/hpf; 2+ = 2/hpf; 3+ = 3/hpf; 4+ = 4 or more/hpf.

Variables entered in model: GA; presence of caries and scabies; quantity of Lactobacillus; severity of Bacteroides/Gardnerella, Mobiluncus, vaginal yeast, and diplococcal infection. Overall model P < 0.0001; VIF = 1.19.

Coded as 0 = absent; 1+ = 1–5/hpf; 2+ = 6–10/hpf; 3+ = 11–20/hpf; 4+ = > 20/hpf.

Variables entered in model: GA; presence of caries and scabies; quantity of Lactobacillus; severity of Bacteroides/Gardnerella, Mobiluncus, vaginal trichomoniasis, and diplococcal infection. Overall model P = 0.015; VIF = 1.08.

Variables entered in model: GA; presence of caries and scabies; quantity of Lactobacillus; severity of Bacteroides/Gardnerella, Mobiluncus, vaginal trichomoniasis, and yeast infection. Overall model P < 0.0001; VIF = 1.11.

Table 6

Multiple ordered logistic regression models for severity of laboratory-diagnosed cervicovaginal infections in 79 lactating Ngäbe women from western Panamá

 OR ± SE95% CIP
Bacterial vaginosis severity*
 Vaginal yeast infection, severity0.30 ± 0.160.10, 0.870.027
Vaginal trichomoniasis severity§
Bacteroides/Gardnerella, severity0.60 ± 0.110.41, 0.880.008
Mobiluncus, severity1.42 ± 0.300.94, 2.140.090
 Vaginal diplococcal infection, severity1.40 ± 0.300.91, 2.140.121
Vaginal yeast infection severity**
 Scabies, presence††8.37 ± 7.531.43, 48.80.018
Lactobacillus, quantity1.86 ± 0.521.07, 3.230.027
Vaginal diplococcal infection severity‡‡∥∥
Bacteroides/Gardnerella, severity0.62 ± 0.120.41, 0.920.019
Lactobacillus, quantity0.18 ± 0.150.04, 0.910.039
 Time after delivery, week0.92 ± 0.040.85, 1.000.055
 Vaginal trichomoniasis, severity1.61 ± 0.470.91, 2.870.102

BV = bacterial vaginosis; CI = confidence interval; hpf = high-power field; OR = odds ratio; SE = standard error; VIF = variance inflation factor.

Severity according to the Nugent score.

Variables entered in model: weeks after delivery; presence of caries and scabies; severity of vaginal trichomoniasis, yeast, and diplococcal infection. Overall model P = 0.023; VIF = 1.00.

Coded as 0 = absent; 1+ = 1/hpf; 2+ = 2/hpf; 3+ = 3/hpf; 4+ = 4 or more/hpf.

Variables entered in model: weeks after delivery; presence of caries and scabies; quantity of Lactobacillus; severity of Bacteroides/Gardnerella, Mobiluncus, vaginal yeast, and diplococcal infection. Overall model P = 0.0043; VIF = 1.13.

Coded as 0 = absent; 1+ = 1–5/hpf; 2+ = 6–10/hpf; 3+ = 11–20/hpf; 4+ = > 20/hpf.

Variables entered in model: weeks after delivery; presence of caries and scabies; quantity of Lactobacillus; severity of Bacteroides/Gardnerella, Mobiluncus, vaginal trichomoniasis, and diplococcal infection. Overall model P = 0.009; VIF = 1.00.

Coded as 0 = absent; 1 = present.

Variables entered in model: weeks after delivery; presence of caries and scabies; quantity of Lactobacillus; severity of Bacteroides/Gardnerella, Mobiluncus, vaginal trichomoniasis, and yeast infection. Overall model P < 0.0001; VIF = 1.05.

A second model for vaginal diplococcal infection including the Nugent score revealed that severity of vaginal diplococcal infection was influenced by weeks after delivery (OR = 0.92 ± 0.03, 95% CI = 0.85, 0.99; P = 0.036); presence of caries (nonsignificant [ns]) and scabies (ns); Nugent score for BV (ns); severity of vaginal trichomoniasis (OR = 1.91 ± 0.51; 95% CI = 1.13, 3.23; P = 0.015) and yeast infection (ns). Overall model P = 0.005, VIF = 1.00.

Severity of vaginal trichomoniasis.

Among pregnant women, the severity of vaginal trichomoniasis was lowered by BV diagnosed by the Nugent score (OR = 0.24, 95% CI = 0.14–0.42) (model not shown). When individual bacteria that contribute to the Nugent score were used (Table 5), the odds of more severe trichomoniasis were increased with more severe diplococcal infection (OR = 1.33, 95% CI = 1.02–1.72) and surprisingly higher quantity of Lactobacillus also increased the odds of more severe trichomoniasis (OR = 1.97, 95% CI = 1.60–2.42). During lactation (Table 6), the odds of more severe vaginal trichomoniasis were lower in mothers with more severe Bacteroides/Gardnerella (OR = 0.60, 95% CI = 0.41–0.88). No variables emerged as significant in the model using the Nugent score (model not shown).

Severity of vaginal yeast infection.

The odds of more severe vaginal yeast infection were higher in those pregnant women with more severe vaginal diplococcal infection both in the model using the Nugent score (OR = 1.34, 95% CI = 1.04–1.73) (model not shown) and in the model using individual BV bacteria (OR = 1.36, 95% CI = 1.02–1.80) where severity of Bacteroides/Gardnerella also increased the odds of more severe vaginal yeast infection (OR = 1.79, 95% CI = 1.05–3.05) (Table 5). During lactation, a different picture emerged. The odds of more severe vaginal yeast infection was higher in mothers with scabies (OR = 6.45, 95% CI = 1.11–37.3) but lower in those with a higher Nugent score (OR = 0.72, 95% CI = 0.52–0.99) (model not shown). When reanalyzed with the individual BV bacteria (Table 6), presence of scabies continued to increase the likelihood of more severe yeast infection (OR = 8.37, 95% CI = 1.43–48.8) and amount of Lactobacillus also increased the likelihood of more severe yeast infection (OR = 1.86, 95% CI = 1.07–3.23).

Severity of vaginal diplococcal infection.

During pregnancy, the risk of more severe diplococcal infection was associated with a higher Nugent score (OR = 20.3, 95% CI = 4.73–87.04) (model not shown). Replacement of the Nugent score with individual BV-associated bacteria (Table 5) revealed a lower odds of more severe diplococcal infection in mothers with more Lactobacillus (OR = 0.26, 95% CI = 0.14–0.47). During lactation (Table 6), more severe diplococcal infection was more likely in mothers with more severe trichomoniasis (OR = 1.91, 95% CI = 1.13–3.23) in a model including the Nugent score (model not shown). However, when the data were reanalyzed with the individual BV-associated bacteria (Table 6), trichomoniasis severity was no longer significant, but both severity of Bacteroides/Gardnerella (OR = 0.62, 95% CI = 0.41–0.92) and amount of Lactobacillus (OR = 0.18, 95% CI = 0.04–0.91) lowered the likelihood of more severe diplococcal infection.

Intestinal nematode epg.

During pregnancy, the multiple linear regression model using the Nugent score revealed that Ascaris epg was higher in pregnant women with AB/UTI (P = 0.031) and with more severe vaginal diplococcal infection (P = 0.011) (model not shown). When BV-associated bacteria were included in the model (Table 7), AB/UTI and diplococcal infection remained significant and the quantity of lactobacilli also emerged as positively associated with Ascaris epg. The positive relationship between hookworm and Trichuris was evident in models for both nematodes (Table 7), and neither model differed when the Nugent score was replaced with BV-associated bacteria. No regression analyses were done for the nematode infections during lactation because of the small number of fecal samples.

Table 7

Final multiple linear regression models on FLOTAC epg for gastrointestinal nematode infections from 72 pregnant Ngäbe women from western Panamá

 β coefficient ± SEP
Ascaris, sqrt epg*
 AB/UTI, presence17.54 ± 6.520.009
 Vaginal diplococcal infection, severity11.16 ± 3.640.003
Lactobacillus, quantity§8.91 ± 3.150.006
Bacteroides/Gardnerella, severity§6.06 ± 3.840.12
 Constant−28.9 ± 15.90.07
Hookworm, sqrt epg
 GA, week0.42 ± 0.230.067
Trichuris, epg0.01 ± 0.002< 0.0001
Mobiluncus, severity§3.52 ± 1.960.077
 Constant−1.26 ± 7.160.861
Trichuris, sqrt epg**
 Hookworm, epg0.004 ± 0.0004< 0.001
 Vaginal trichomoniasis, severity2.02 ± 1.160.085
 Constant−1.70 ± 1.660.309

AB/UTI = asymptomatic bacteriuria/urinary tract infection; GA = gestational age; hpf = high-power field; sqrt epg = square root transformed eggs per gram; VIF = variance inflation factor.

Variables entered in model: GA, presence of caries, scabies, and AB/UTI; amount of Lactobacillus; severity of Bacteroides/Gardnerella, Mobiluncus, vaginal trichomoniasis, yeast and diplococcal infection; hookworm and Trichuris epg. Overall model F4,67 = 5.56; P = 0.0006; adjusted R2 = 0.20; VIF = 1.58.

Coded as 0 = absent, 1 = present.

Coded as 0 = absent; 1+ = 1/hpf; 2+ = 2/hpf; 3+ = 3/hpf; 4+ = 4 or more/hpf.

Coded as 0 = absent; 1+ = 1–5/hpf; 2+ = 6–10/hpf; 3+ = 11–20/hpf; 4+ = > 20/hpf.

Variables entered in model: GA, presence of caries, scabies, and AB/UTI; amount of Lactobacillus; severity of Bacteroides/Gardnerella, Mobiluncus, vaginal trichomoniasis, yeast, and diplococcal infection; Ascaris and Trichuris epg. Overall model F3,68 = 16.58; P < 0.0001; adjusted R2 = 0.39; VIF = 1.01.

Variables entered in model: GA, presence of caries, scabies, and AB/UTI; amount of Lactobacillus; severity of Bacteroides/Gardnerella, Mobiluncus, vaginal trichomoniasis, yeast, and diplococcal infection; Ascaris and hookworm epg. Overall model F2,69 = 49.45; P < 0.0001; adjusted R2 = 0.58; VIF = 1.00.

A composite picture.

Within the vaginal tract, positive associations were detected among severity of vaginal yeast, diplococcal infection, and trichomoniasis (Figure 2). A complexity emerged as we explored the role of bacteria morphotypes included in the Nugent score diagnosis of BV. During pregnancy, the amount of Lactobacillus was associated with less severe diplococcal infection but with more severe vaginal trichomoniasis (Figure 2A). During lactation, the amount of Lactobacillus lowered the odds of more severe diplococcal infection but increased the odds of more severe vaginal yeast infection (Figure 2B). The presence of Bacteroides/Gardnerella increased the odds of more severe vaginal yeast infection during pregnancy (Figure 2A) but reduced the odds of more severe trichomoniasis and diplococcal infection during lactation (Figure 2B).

Figure 2.
Figure 2.

Relationships among infections of the vaginal tract (Nugent score for bacterial vaginosis as well as component bacteria shown in dashed boxes [Bacteroides/Gardnerella, Mobiluncus, and Lactobacillus], trichomoniasis, yeast, diplococcal), urinary tract (AB/UTI), intestine (hookworm, Trichuris, Ascaris), and skin (scabies, impetigo) in pregnant (A) and lactating (B) Ngäbe women from western Panamá. Associations based on multiple regression analysis (P < 0.05) are indicated as positive () or negative (). Associations emerging from χ2 analysis are indicated as more () or less () than expected by chance (P < 0.005).

Citation: The American Society of Tropical Medicine and Hygiene 92, 6; 10.4269/ajtmh.14-0547

The vaginal microflora was also associated with infections beyond the vaginal tract. In pregnancy, the quantity of Lactobacillus and severity of diplococcal infection were positively associated with Ascaris epg, AB/UTI was associated with more severe trichomoniasis but lower quantity of Lactobacillus (Figure 2A); and during lactation, the odds of AB/UTI were higher in women with higher quantity of Mobiluncus (Figure 2B).

Discussion

Constraints on primary health care for vulnerable pregnant and lactating women living in remote areas of developing countries typically limit the possibility of screening for many infections. This study of pregnant and lactating women revealed the wide diversity of neglected infections in this extremely impoverished, rural, and indigenous population. Of particular note were the high prevalences of Trichomonas vaginalis (> 70%), BV (∼60%), AB/UTI (> 35%), and hookworm (> 45%) in pregnancy and lactation as well as caries, scabies, vaginal yeast, and vaginal diplococcal infection at prevalences between 10% and 30%. Vaginal yeast infection was more common in pregnancy than lactation whereas vaginal diplococcal infection was less common but more severe in pregnancy. This preliminary descriptive study reveals several potential associations, both positive and negative, among pathogens that should be explored further. If confirmed, the findings highlight the need for appropriate management, in particular, of vaginal infections.

In comparing frequency and severity of infections between pregnant and lactating women, our observations were consistent with known physiological and hormonal differences. During pregnancy, higher levels of estradiol and higher glycogen content in vaginal secretions have been associated with vulvovaginal yeast,59 and may similarly explain our finding that vaginal yeast was more prevalent during pregnancy than lactation. Elevated progesterone has been shown to facilitate diplococcal replication,60 which could account for our finding of a more severe, though less prevalent, diplococcal infection in pregnancy compared with lactation. During normal pregnancy, the vaginal bacterial flora has been shown to be dominated by Lactobacillus61 whereas, during lactation, disruption of this balance has been associated with decrease in the number of Lactobacillus.62 This was consistent with our finding that Lactobacillus was more common in pregnancy than lactation. To our knowledge, ours is the first report of a higher prevalence of scabies during pregnancy than lactation.

With regard to associations among vaginal infections, BV has been reported to co-occur with Trichomonas in nonpregnant women.6366 However, we observed that a higher severity of trichomoniasis was associated with lower severity of BV (but higher quantity of Lactobacillus) during pregnancy. To our knowledge, this has not been previously reported, and suggests that Lactobacillus may not be protective against trichomoniasis during pregnancy.

Furthermore, our results suggest both positive and negative associations of Lactobacillus with local as well as systemic infections, as higher quantities of vaginal lactobacilli were associated with reduced odds of diplococcal infection in both pregnant and lactating women and reduced the odds of AB/UTI in pregnancy, but with higher intestinal Ascaris epg during pregnancy and more severe vaginal yeast infection during lactation. Orally administered lactobacilli have been shown to have immunomodulatory and oxidative properties in the urinary tract, and to decrease vaginal pH.67 Lactobacillus has also been shown to inhibit pathogen adherence.68 On the other hand, Lactobacillus was reported to be dominant within the vaginal microbiome of nonpregnant Chinese women who had vulvovaginal yeast infection,69 suggesting that its presence increased the risk of yeast infection. Furthermore, Lactobacillus casei increased the susceptibility of rodents to intestinal nematodes,70 whereas Lactobacillus rhamnosus reduced the duration of nematode infection.71 Our findings suggest that vaginal Lactobacillus may increase susceptibility to Ascaris or prolong duration of infection, an observation not previously reported.

Soil-transmitted nematodes are known not only to co-occur in pregnant women72 and women of reproductive age73 but also to co-occur more frequently than expected by chance in age-adjusted data from a rural community in Brazil.74 This co-occurrence is typically explained by common exposure routes, common household factors, common immune response mechanisms, common host genetics, or facilitated establishment in the presence of the other pathogen.75,76 Our data similarly revealed co-occurrence of Trichuris with hookworm, but Ascaris was not associated with hookworm or Trichuris in either χ2 tests or in the multiple regression models of epg. This is consistent with our recent finding that high-prevalence spatial clusters of Ascaris did not overlap with those of Trichuris or hookworm in Panamanian preschool children.77 Interestingly, Ascaris epg was positively associated the presence of AB/UTI, the quantity of vaginal lactobacilli, and the severity of vaginal diplococcal infection. To our knowledge, these associations have not been previously reported.

This study had several strengths. Despite the remote location and the limited health facilities, a range of infections was detected using a clinical approach together with basic laboratory assays. The absence of malaria and HIV in this population allowed us to explore relationships among the more neglected vaginal infections, skin and oral infections, as well as intestinal nematodes. By using multiple diagnostic methods for the intestinal nematodes and for AB/UTI, we reduced the likelihood that misclassification error resulted in spurious associations.78

We also acknowledge several limitations. Our cross-sectional design precluded examination of causation. Although we were able to recruit approximately 90% of eligible women, without a full census of the catchment area, we cannot rule out selection bias. It was difficult to obtain fecal samples from the women who visited the health center only once. It is more difficult to detect negative associations than positive associations using standard statistical approaches.79 Urine culture would have allowed us to establish the etiology of AB/UTI. Nucleic acid amplification tests would have allowed us to confirm if intracellular diplococci were Neisseria gonorrhoeae and to determine if Chlamydia was prevalent in this population (suspected based on our clinical findings, morphology of epithelial cells, and the presence of abundant leukocytes in the gram-stained vaginal smears80).

Our findings have several implications for clinical care of this vulnerable population. Presumably healthy women with no evident physical distress had a multiplicity of conditions that together may have serious implications for maternal, fetal, and infant health. Efforts to prevent infection including improvements in hygiene, water and sanitation are needed. Sexual transmission may account for many of the vaginal infections and possibly the skin and oral infections. With awareness of vaginal infections, women may be more receptive to discussions about reproductive health. Given the very high occurrence of vaginal infections, screening should be a routine part of prenatal care. To this end, health centers need to provide privacy for cervicovaginal exams and provide pathogen-specific differential diagnosis rather than clinically based management to prevent inappropriate or partial treatment of underlying pathologies. Until this is possible, new diagnostic protocols based on local epidemiology are urgently needed for the treatment of infectious diseases in pregnant and lactating women of the Ngäbe community. Finally, further research is needed to confirm both positive and negative associations reported here, to ensure appropriate management of co-occurring infections.

ACKNOWLEDGMENTS

Community health workers and traditional midwives actively participated in the recruitment process. The Maternal-Infant Program of the Ngäbe-Comarcal Regional Health Department (Ministry of Health) helped to coordinate rural visits, collect clinical data and biological samples. They also provided clinical advice to participants. Laboratory technicians and laboratory assistants at the “Hospital General del Oriente Chiricano” in San Félix (Chiriquí, Panamá) assisted in collecting samples and conducting interviews. They processed urine samples and did Kato-Katz and FLOTAC analysis of fecal samples. We extend a special thanks to all mothers who participated in the study.

  • 1.

    Anderson MR, Klink K, Cohrssen A, 2004. Evaluation of vaginal complaints. JAMA 291: 13681379.

  • 2.

    Ilkit M, Guzel AB, 2011. The epidemiology, pathogenesis, and diagnosis of vulvovaginal candidosis: a mycological perspective. Crit Rev Microbiol 37: 250261.

    • Search Google Scholar
    • Export Citation
  • 3.

    Schnarr J, Smaill F, 2008. Asymptomatic bacteriuria and symptomatic urinary tract infections in pregnancy. Eur J Clin Invest 38 (Suppl 2): 5057.

    • Search Google Scholar
    • Export Citation
  • 4.

    Larocque R, Casapia M, Gotuzzo E, Gyorkos TW, 2005. Relationship between intensity of soil-transmitted helminth infections and anemia during pregnancy. Am J Trop Med Hyg 73: 783789.

    • Search Google Scholar
    • Export Citation
  • 5.

    Kandan PM, Menaga V, Kumar RR, 2011. Oral health in pregnancy (guidelines to gynaecologists, general physicians and oral health care providers). J Pak Med Assoc 61: 10091014.

    • Search Google Scholar
    • Export Citation
  • 6.

    Matevosyan NR, 2011. Periodontal disease and perinatal outcomes. Arch Gynecol Obstet 283: 675686.

  • 7.

    Feldmeier H, Heukelbach J, 2009. Epidermal parasitic skin diseases: a neglected category of poverty-associated plagues. Bull World Health Organ 87: 152159.

    • Search Google Scholar
    • Export Citation
  • 8.

    Afsar FS, 2010. Skin infections in developing countries. Curr Opin Pediatr 22: 459466.

  • 9.

    Zhang D, Mi L, Yang H, 2014. Incidence and factors influencing postpartum bacterial vaginosis: a controlled study. Chin Med J (Engl) 127: 586587.

    • Search Google Scholar
    • Export Citation
  • 10.

    Adriaens LM, Alessandri R, Sporri S, Lang NP, Persson GR, 2009. Does pregnancy have an impact on the subgingival microbiota? J Periodontol 80: 7281.

    • Search Google Scholar
    • Export Citation
  • 11.

    Moodley D, Esterhuizen T, Reddy L, Moodley P, Singh B, Ngaleka L, Govender D, 2011. Incident HIV infection in pregnant and lactating women and its effect on mother-to-child transmission in South Africa. J Infect Dis 203: 12311234.

    • Search Google Scholar
    • Export Citation
  • 12.

    Selvaraj S, Paintsil E, 2013. Virologic and host risk factors for mother-to-child transmission of HIV. Curr HIV Res 11: 93101.

  • 13.

    Schleiss MR, 2006. Role of breast milk in acquisition of cytomegalovirus infection: Recent advances. Curr Opin Pediatr 18: 4852.

  • 14.

    Amir LH, Cullinane M, Garland SM, Tabrizi SN, Donath SM, Bennett CM, Cooklin AR, Fisher JR, Payne MS, 2011. The role of micro-organisms (Staphylococcus aureus and Candida albicans) in the pathogenesis of breast pain and infection in lactating women: study protocol. BMC Pregnancy Childbirth 11: 54.

    • Search Google Scholar
    • Export Citation
  • 15.

    Betzold CM, 2012. Results of microbial testing exploring the etiology of deep breast pain during lactation: a systematic review and meta-analysis of nonrandomized trials. J Midwifery Womens Health 57: 353364.

    • Search Google Scholar
    • Export Citation
  • 16.

    Elram T, Livne A, Oren A, Gross I, Shapiro M, Mankuta D, 2008. Labor as a bacteriuric event—assessment and risk factors. J Matern Fetal Neonatal Med 21: 483486.

    • Search Google Scholar
    • Export Citation
  • 17.

    Knowles S, O'Sullivan N, Meenan A, Hanniffy R, Robson M, 2014. Maternal sepsis incidence, aetiology and outcome for mother and fetus: a prospective study. BJOG 121: 17541755.

    • Search Google Scholar
    • Export Citation
  • 18.

    Muhangi L, Woodburn P, Omara M, Omoding N, Kizito D, Mpairwe H, Nabulime J, Ameke C, Morison LA, Elliott AM, 2007. Associations between mild-to-moderate anaemia in pregnancy and helminth, malaria and HIV infection in Entebbe, Uganda. Trans R Soc Trop Med Hyg 101: 899907.

    • Search Google Scholar
    • Export Citation
  • 19.

    Adegnika AA, Ramharter M, Agnandji ST, Ateba Ngoa U, Issifou S, Yazdanbahksh M, Kremsner PG, 2010. Epidemiology of parasitic co-infections during pregnancy in Lambarene, Gabon. Trop Med Int Health 15: 12041209.

    • Search Google Scholar
    • Export Citation
  • 20.

    Ivan E, Crowther NJ, Rucogoza AT, Osuwat LO, Munyazesa E, Mutimura E, Njunwa KJ, Zambezi KJ, Grobusch MP, 2012. Malaria and helminthic co-infection among HIV-positive pregnant women: prevalence and effects of antiretroviral therapy. Acta Trop 124: 179184.

    • Search Google Scholar
    • Export Citation
  • 21.

    Liabsuetrakul T, Chaikongkeit P, Korviwattanagarn S, Petrueng C, Chaiya S, Hanvattanakul C, Kongkitkul P, Sinthuuthai C, Kalong N, Ongsawang D, Ungsathapornpon S, Ameeroh A, Bavonnarongdet P, Buadung A, 2009. Epidemiology and the effect of treatment of soil-transmitted helminthiasis in pregnant women in southern Thailand. Southeast Asian J Trop Med Public Health 40: 211222.

    • Search Google Scholar
    • Export Citation
  • 22.

    Franklin TL, Monif GR, 2000. Trichomonas vaginalis and bacterial vaginosis. Coexistence in vaginal wet mount preparations from pregnant women. J Reprod Med 45: 131134.

    • Search Google Scholar
    • Export Citation
  • 23.

    Goto A, Nguyen QV, Pham NM, Kato K, Cao TP, Le TH, Hoang QK, Le TQ, Nguyen BT, Katsube M, Ishii S, Yasumura S, 2005. Prevalence of and factors associated with reproductive tract infections among pregnant women in ten communes in Nghe An province, Vietnam. J Epidemiol 15: 163172.

    • Search Google Scholar
    • Export Citation
  • 24.

    Romoren M, Sundby J, Velauthapillai M, Rahman M, Klouman E, Hjortdahl P, 2007. Chlamydia and gonorrhoea in pregnant Batswana women: time to discard the syndromic approach? BMC Infect Dis 7: 27.

    • Search Google Scholar
    • Export Citation
  • 25.

    Lello J, Knopp S, Mohammed KA, Khamis IS, Utzinger J, Viney ME, 2013. The relative contribution of co-infection to focal infection risk in children. Proc Biol Sci 280: 20122813.

    • Search Google Scholar
    • Export Citation
  • 26.

    Cauci S, Culhane JF, 2007. Modulation of vaginal immune response among pregnant women with bacterial vaginosis by Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhoeae, and yeast. Am J Obstet Gynecol 196: 133.e1133.e7.

    • Search Google Scholar
    • Export Citation
  • 27.

    Allsworth JE, Peipert JF, 2011. Severity of bacterial vaginosis and the risk of sexually transmitted infection. Am J Obstet Gynecol 205: 113.e1113.e6.

    • Search Google Scholar
    • Export Citation
  • 28.

    Balkus JE, Richardson BA, Rabe LK, Taha TE, Mgodi N, Kasaro MP, Ramjee G, Hoffman IF, Abdool Karim SS, 2014. Bacterial vaginosis and the risk of Trichomonas vaginalis acquisition among HIV-1-negative women. Sex Transm Dis 41: 123128.

    • Search Google Scholar
    • Export Citation
  • 29.

    Ezenwa VO, Jolles AE, 2011. From host immunity to pathogen invasion: the effects of helminth coinfection on the dynamics of microparasites. Integr Comp Biol 51: 540551.

    • Search Google Scholar
    • Export Citation
  • 30.

    Friberg IM, Little S, Ralli C, Lowe A, Hall A, Jackson JA, Bradley JE, 2013. Macroparasites at peripheral sites of infection are major and dynamic modifiers of systemic antimicrobial pattern recognition responses. Mol Ecol 22: 28102826.

    • Search Google Scholar
    • Export Citation
  • 31.

    Getachew M, Tafess K, Zeynudin A, Yewhalaw D, 2013. Prevalence of soil transmitted helminthiasis and malaria co-infection among pregnant women and risk factors in Gilgel Gibe Dam area, southwest Ethiopia. BMC Res Notes 6: 263.

    • Search Google Scholar
    • Export Citation
  • 32.

    Hartgers FC, Yazdanbakhsh M, 2006. Co-infection of helminths and malaria: modulation of the immune responses to malaria. Parasite Immunol 28: 497506.

    • Search Google Scholar
    • Export Citation
  • 33.

    Supali T, Verweij JJ, Wiria AE, Djuardi Y, Hamid F, Kaisar MM, Wammes LJ, van Lieshout L, Luty AJ, Sartono E, Yazdanbakhsh M, 2010. Polyparasitism and its impact on the immune system. Int J Parasitol 40: 11711176.

    • Search Google Scholar
    • Export Citation
  • 34.

    Graham AL, Cattadori IM, Lloyd-Smith JO, Ferrari MJ, Bjornstad ON, 2007. Transmission consequences of coinfection: cytokines writ large? Trends Parasitol 23: 284291.

    • Search Google Scholar
    • Export Citation
  • 35.

    Fenton A, 2013. Dances with worms: the ecological and evolutionary impacts of deworming on coinfecting pathogens. Parasitology 140: 11191132.

    • Search Google Scholar
    • Export Citation
  • 36.

    Singer M, 2013. Development, coinfection, and the syndemics of pregnancy in sub-Saharan Africa. Infect Dis Poverty 2: 26.

  • 37.

    Sistema de Naciones Unidas, Gobierno de la República de Panamá, 2009. Objetivos de desarrollo del Milenio, III Informe de Panamá, 2009, 1st Ed. Apartadó, República de Panamá: El PNUD en Panamá, 2736.

    • Search Google Scholar
    • Export Citation
  • 38.

    Kuamri A, Goswami S, Mukherjee P, 2013. Comparative study of various methods of fetal weight estimation in term pregnancy. South Asian Feder Obst Gynae 5: 2225.

    • Search Google Scholar
    • Export Citation
  • 39.

    Fescina RH, De Mucio B, Martínez G, Alemán A, Sosa C, Mainero L, Rubino M, 2011. Monitoring Fetal Growth: Self-Instruction Manual, 2nd Ed. Montevideo, Uruguay: PAHO, 1619.

    • Search Google Scholar
    • Export Citation
  • 40.

    IOM and NRC, 2009. Weight Gain during Pregnancy: Reexamining the Guidelines. Washington, DC: The National Academies Press, 868.

  • 41.

    ACOG, 2002. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. Obstet Gynecol 99: 159167.

    • Search Google Scholar
    • Export Citation
  • 42.

    Hunter JM, Arbona SI, 1995. The tooth as a marker of developing world quality of life: a field study in Guatemala. Soc Sci Med 41: 12171240.

    • Search Google Scholar
    • Export Citation
  • 43.

    Simel DL, Rennie D, 2009. The Rational Clinical Examination: Evidence-Based Clinical Diagnosis. New York, NY: McGraw Hill / JAMA Evidence, 774.

    • Search Google Scholar
    • Export Citation
  • 44.

    Hicks MI, Elston DM, 2009. Scabies. Dermatol Ther 22: 279292.

  • 45.

    Lazar AJF, 2007. The skin. Kumar V, Abbas AK, Fausto N, Mitchell R, eds. Robbins Basic Pathology, 8th Ed. Philadelphia, PA: Elsevier Health Sciences, 843844.

    • Search Google Scholar
    • Export Citation
  • 46.

    Ollendorff AT, 2012. Cervicitis Clinical Presentation. Medscape. Available at: http://emedicine.medscape.com/article/253402-clinical-a0256. Accessed June 12, 2014.

    • Search Google Scholar
    • Export Citation
  • 47.

    Ryan CA, Courtois BN, Hawes SE, Stevens CE, Eschenbach DA, Holmes KK, 1998. Risk assessment, symptoms, and signs as predictors of vulvovaginal and cervical infections in an urban US STD clinic: implications for use of STD algorithms. Sex Transm Infect 74 (Suppl 1): S59S76.

    • Search Google Scholar
    • Export Citation
  • 48.

    Hainer BL, Gibson MV, 2011. Vaginitis. Am Fam Physician 83: 807815.

  • 49.

    Patil MJ, Nagamoti JM, Metgud SC, 2012. Diagnosis of Trichomonas vaginalis from vaginal specimens by wet mount microscopy, in pouch TV culture system, and PCR. J Glob Infect Dis 4: 2225.

    • Search Google Scholar
    • Export Citation
  • 50.

    Nugent RP, Krohn MA, Hillier SL, 1991. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J Clin Microbiol 29: 297301.

    • Search Google Scholar
    • Export Citation
  • 51.

    Coppolillo EF, Perazzi BE, Famiglietti AM, Cora Eliseht MG, Vay CA, Barata AD, 2003. Diagnosis of bacterial vaginosis during pregnancy. J Low Genit Tract Dis 7: 117121.

    • Search Google Scholar
    • Export Citation
  • 52.

    Deville WL, Yzermans JC, van Duijn NP, Bezemer PD, van der Windt DA, Bouter LM, 2004. The urine dipstick test useful to rule out infections. A meta-analysis of the accuracy. BMC Urol 4: 4.

    • Search Google Scholar
    • Export Citation
  • 53.

    Simerville JA, Maxted WC, Pahira JJ, 2005. Urinalysis: a comprehensive review. Am Fam Physician 71: 11531162.

  • 54.

    Caron F, 2010. Diagnosis and treatment of community-acquired urinary tract infections in adults: what has changed. Comments on the 2008 guidelines of the French health products safety agency (AFSSAPS). Presse Med 39: 4248.

    • Search Google Scholar
    • Export Citation
  • 55.

    WHO, 1991. Basic Laboratory Methods in Medical Parasitology, 1st Ed. England, United Kingdom: World Health Organization, 2528.

  • 56.

    Cringoli G, Rinaldi L, Maurelli MP, Utzinger J, 2010. FLOTAC: new multivalent techniques for qualitative and quantitative copromicroscopic diagnosis of parasites in animals and humans. Nat Protoc 5: 503515.

    • Search Google Scholar
    • Export Citation
  • 57.

    Knopp S, Speich B, Hattendorf J, Rinaldi L, Mohammed KA, Khamis IS, Mohammed AS, Albonico M, Rollinson D, Marti H, Cringoli G, Utzinger J, 2011. Diagnostic accuracy of Kato-Katz and FLOTAC for assessing anthelmintic drug efficacy. PLoS Negl Trop Dis 5: e1036.

    • Search Google Scholar
    • Export Citation
  • 58.

    Hellard E, Pontier D, Sauvage F, Poulet H, Fouchet D, 2012. True versus false parasite interactions: a robust method to take risk factors into account and its application to feline viruses. PLoS ONE 7: e29618.

    • Search Google Scholar
    • Export Citation
  • 59.

    Soong D, Einarson A, 2009. Vaginal yeast infections during pregnancy. Can Fam Physician 55: 255256.

  • 60.

    Edwards JL, 2010. Neisseria gonorrhoeae survival during primary human cervical epithelial cell infection requires nitric oxide and is augmented by progesterone. Infect Immun 78: 12021213.

    • Search Google Scholar
    • Export Citation
  • 61.

    Chandiramani M, Lee Y, Kindinger L, Arulkumaran S, Marchesi J, Holmes E, Nicholson J, Teoh T, MacIntyre D, Bennett P, 2014. The evolution of the vaginal microbiome throughout uncomplicated pregnancy in a UK population. Arch Dis Child Fetal Neonatal Ed 99 (Suppl 1): A12A13.

    • Search Google Scholar
    • Export Citation
  • 62.

    Yang XL, Yang HX, Duan T, He J, Sun LZ, Yu YH, Liu XH, Li XM, 2009. Vaginal microflora and relevant factors in puerperium. Zhonghua Fu Chan Ke Za Zhi 44: 496499.

    • Search Google Scholar
    • Export Citation
  • 63.

    Demirezen S, Korkmaz E, Beksac MS, 2005. Association between trichomoniasis and bacterial vaginosis: examination of 600 cervicovaginal smears. Cent Eur J Public Health 13: 9698.

    • Search Google Scholar
    • Export Citation
  • 64.

    Heller DS, Maslyak S, Skurnick J, 2006. Is the presence of Trichomonas on a Pap smear associated with an increased incidence of bacterial vaginosis? J Low Genit Tract Dis 10: 137139.

    • Search Google Scholar
    • Export Citation
  • 65.

    Uma S, Balakrishnan P, Murugavel KG, Srikrishnan AK, Kumarasamy N, Anand S, Cecelia JA, Celentano D, Mayer KH, Thyagarajan SP, Solomon S, 2006. Bacterial vaginosis in women of low socioeconomic status living in slum areas in Chennai, India. Sex Health 3: 297298.

    • Search Google Scholar
    • Export Citation
  • 66.

    Brotman RM, Klebanoff MA, Nansel TR, Yu KF, Andrews WW, Zhang J, Schwebke JR, 2010. Bacterial vaginosis assessed by gram stain and diminished colonization resistance to incident gonococcal, chlamydial, and trichomonal genital infection. J Infect Dis 202: 19071915.

    • Search Google Scholar
    • Export Citation
  • 67.

    Amdekar S, Singh V, Singh DD, 2011. Probiotic therapy: immunomodulating approach toward urinary tract infection. Curr Microbiol 63: 484490.

  • 68.

    Cadieux PA, Burton J, Devillard E, Reid G, 2009. Lactobacillus by-products inhibit the growth and virulence of uropathogenic Escherichia coli. J Physiol Pharmacol 60 (Suppl 6): 1318.

    • Search Google Scholar
    • Export Citation
  • 69.

    Liu MB, Xu SR, He Y, Deng GH, Sheng HF, Huang XM, Ouyang CY, Zhou HW, 2013. Diverse vaginal microbiomes in reproductive-age women with vulvovaginal candidiasis. PLoS ONE 8: e79812.

    • Search Google Scholar
    • Export Citation
  • 70.

    Dea-Ayuela MA, Rama-Iniguez S, Bolas-Fernandez F, 2008. Enhanced susceptibility to Trichuris muris infection of B10Br mice treated with the probiotic Lactobacillus casei. Int Immunopharmacol 8: 2835.

    • Search Google Scholar
    • Export Citation
  • 71.

    McClemens J, Kim JJ, Wang H, Mao YK, Collins M, Kunze W, Bienenstock J, Forsythe P, Khan WI, 2013. Lactobacillus rhamnosus ingestion promotes innate host defense in an enteric parasitic infection. Clin Vaccine Immunol 20: 818826.

    • Search Google Scholar
    • Export Citation
  • 72.

    Yatich NJ, Funkhouser E, Ehiri JE, Agbenyega T, Stiles JK, Rayner JC, Turpin A, Ellis WO, Jiang Y, Williams JH, Afriyie-Gwayu E, Phillips T, Jolly PE, 2010. Malaria, intestinal helminths and other risk factors for stillbirth in Ghana. Infect Dis Obstet Gynecol 2010: 350763.

    • Search Google Scholar
    • Export Citation
  • 73.

    Nguyen PH, Nguyen KC, Nguyen TD, Le MB, Bern C, Flores R, Martorell R, 2006. Intestinal helminth infections among reproductive age women in Vietnam: prevalence, co-infection and risk factors. Southeast Asian J Trop Med Public Health 37: 865874.

    • Search Google Scholar
    • Export Citation
  • 74.

    Fleming FM, Brooker S, Geiger SM, Caldas IR, Correa-Oliveira R, Hotez PJ, Bethony JM, 2006. Synergistic associations between hookworm and other helminth species in a rural community in Brazil. Trop Med Int Health 11: 5664.

    • Search Google Scholar
    • Export Citation
  • 75.

    Bethony J, Brooker S, Albonico M, Geiger SM, Loukas A, Diemert D, Hotez PJ, 2006. Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm. Lancet 367: 15211532.

    • Search Google Scholar
    • Export Citation
  • 76.

    Scott ME, 2008. Ascaris lumbricoides: a review of its epidemiology and relationship to other infections. Ann Nestlé 66: 1127.

  • 77.

    Halpenny CM, Paller C, Koski KG, Valdes VE, Scott ME, 2013. Regional, household and individual factors that influence soil transmitted helminth reinfection dynamics in preschool children from rural indigenous Panama. PLoS Negl Trop Dis 7: e2070.

    • Search Google Scholar
    • Export Citation
  • 78.

    Tarafder MR, Carabin H, McGarvey ST, Joseph L, Balolong E Jr, Olveda R, 2011. Assessing the impact of misclassification error on an epidemiological association between two helminthic infections. PLoS Negl Trop Dis 5: e995.

    • Search Google Scholar
    • Export Citation
  • 79.

    Fenton A, Viney ME, Lello J, 2010. Detecting interspecific macroparasite interactions from ecological data: patterns and process. Ecol Lett 13: 606615.

    • Search Google Scholar
    • Export Citation
  • 80.

    Myziuk L, Romanowski B, Brown M, 2001. Endocervical gram stain smears and their usefulness in the diagnosis of Chlamydia trachomatis. Sex Transm Infect 77: 103106.

    • Search Google Scholar
    • Export Citation

Author Notes

* Address correspondence to Marilyn E. Scott, Institute of Parasitology and Centre for Host-Parasite Interactions, McGill University (Macdonald Campus), 21,111 Lakeshore Road, Ste-Anne de Bellevue, Quebec, Canada H9X 3V9. E-mail: marilyn.scott@mcgill.ca

Financial support: This research was funded by the Panamanian “Secretaría Nacional de Ciencia, Tecnología e Innovación” (SENACYT COL08-009). Research at the Institute of Parasitology, McGill University is supported by the Fonds FQRNT.

Authors' addresses: Doris González-Fernández and Marilyn E. Scott, Institute of Parasitology and Centre for Host-Parasite Interactions, McGill University (Macdonald Campus), Ste-Anne de Bellevue, Quebec, Canada, E-mails: doris.gonzalez-fernandez@mail.mcgill.ca and marilyn.scott@mcgill.ca. Kristine G. Koski, School of Dietetics and Human Nutrition and Centre for Host-Parasite Interactions, McGill University (Macdonald Campus), Ste-Anne de Bellevue, Quebec, Canada, E-mail: kris.koski@mcgill.ca. Odalis Teresa Sinisterra, Department of Nutritional Health, Provision of Health Services Direction, Ministry of Health, Republic of Panamá, E-mail: odalisin@gmail.com. Emérita del Carmen Pons, Coordination of Nutritional Biochemistry for Research, Department of Nutritional Health, Provision of Health Services Direction, Ministry of Health, Republic of Panamá, E-mail: emeritapons@gmail.com. Enrique Murillo, Department of Biochemistry, Faculty of Natural, Exact Sciences and Technology, University of Panamá, Panamá, E-mail: emurillo29@hotmail.com.

Save