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Perinatal malaria and tuberculosis co-infection: A case report
International Journal of Infectious Diseases 14 (2010) e254–e256
Contents lists available at ScienceDirect
International Journal of Infectious Diseases journal homepage: www.elsevier.com/locate/ijid
Case Report
Perinatal malaria and tuberculosis co-infection: A case report Rajoo Thapa *, Debkrishna Mallick, Biswajit Biswas The Department of Pediatrics and Division of Neonatology, The Institute of Child Health, 11, Dr. Biresh Guha Street, Kolkata-700017, West Bengal, India
A R T I C L E I N F O
A B S T R A C T
Article history: Received 31 August 2008 Received in revised form 9 April 2009 Accepted 17 April 2009
India remains endemic for both vivax malaria and tuberculosis. In spite of the high burden of tuberculosis in the country, reports on congenital tuberculosis in the literature are limited. We report herein an unusual instance of co-occurrence of perinatal falciparum malaria and tuberculosis in a 34day-old female newborn, who presented with symptoms of sepsis. The diagnosis was based on the demonstration of Plasmodium falciparum on peripheral blood smear and tubercle bacilli in gastric aspirate samples. The maternal history for falciparum malaria was positive during her eighth month of pregnancy and the father was an open case of sputum smear-positive pulmonary tuberculosis. She responded dramatically to combined antimalarial and antitubercular chemotherapy. A search for combined etiologies in presumed ‘sepsis’ in the newborn, guided by history, physical examination, and laboratory investigations, is warranted. ß 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Corresponding Editor: William Cameron, Ottawa, Canada Keywords: Perinatal falciparum malaria Perinatal tuberculosis Sepsis Antimalarial chemotherapy Antitubercular chemotherapy
1. Introduction Both congenital tuberculosis and congenital malaria are rarely diagnosed, even in countries endemic for the adult forms of the diseases. The presentation is usually with non-specific signs and symptoms. A meticulous past medical history, including that of the maternal gestation and family members is often the initial suspicion-arousing event. Both the diseases are associated with extremely high mortality in the absence of timely recognition and prompt therapy. We report an unusual case of a 34-day-old female newborn with co-occurrence of perinatal falciparum malaria and tuberculosis, suspected primarily on the basis of positive maternal and family history. She responded dramatically to combined antimalarial and antitubercular therapy. 2. Case report A 34-day-old, term, female infant, born to non-consanguineous parents was initially seen for a three-day history of cough and progressive lethargy, with poor breastfeeding and fever. The mother also noted that the baby had turned progressively paler over the last week. There was no history of abdominal distension, oliguria, alteration of consciousness, convulsions, or prolonged jaundice in the neonatal period. She was delivered at home by a traditional birth attendant, by spontaneous vaginal delivery, and
* Corresponding author. Tel.: +91 33 22905686; fax: +91 33 22475686. E-mail address: [email protected] (R. Thapa).
there had been no immediate postnatal complications. She was not immunized at birth. The mother’s past medical history was significant for an episode of fever due to falciparum malaria at eight months of gestation, which had been treated with chloroquine, but unfortunately not as per the recommendations of the National Malaria Eradication Programme, Department of Health and Family Welfare, Government of India. Besides this, she denied any other illnesses during her gestation or in the immediate past. The father was an open case of sputum smear-positive pulmonary tuberculosis (PTB) with a suggestive chest radiograph, diagnosed a month previously and was on intensive phase antitubercular chemotherapy (isoniazid, rifampin, pyrazinamide, and ethambutol) with partial response. At the time of the baby’s admission, the father’s sputum remained positive for acid-fast bacilli (AFB; graded as 1+ (10–99 AFB per 100 fields examined) as per the guidelines of the International Union Against Tuberculosis and Lung Disease (IUATLD)1). On examination, the infant appeared pale, dehydrated, and tachypneic with labored breathing. She weighed 2.5 kg and measured 53 cm in length (both below the third percentile for age and sex). The rectal temperature was 39 8C, and she had a heart rate of 194 per minute, a respiratory rate of 86 per minute, and an oxygen saturation of 87% in room air. Moderate intercostal, suprasternal, and subcostal chest retractions were noted. The chest auscultation revealed bilateral, diffuse crepitations with occasional rales. The liver and the spleen were palpable 3.5 cm and 3 cm below the right and the left costal margins, respectively. Examination of the other major systems was non-contributory. A complete hemogram showed the following: hemoglobin 6.2 g/dl,
1201-9712/$36.00 – see front matter ß 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ijid.2009.04.005
R. Thapa et al. / International Journal of Infectious Diseases 14 (2010) e254–e256
e255
same for CSF was negative. The mother did not consent to invasive diagnostic procedures for the exclusion of genitourinary tuberculosis; however her urine sample cultures for AFB on two occasions were negative. She was started on a four-drug regimen comprising isoniazid, rifampin, pyrazinamide, and streptomycin, at the recommended doses. The infant improved dramatically on combined antimalarial and antitubercular therapy. At 12 weeks of follow-up, she showed remarkable weight gain and was developing normally with age-appropriate anthropometry. At the time of writing, she was on chemotherapy with two drugs, isoniazid and rifampin. 3. Discussion
Figure 1. Chest radiograph of the newborn showing diffuse miliary changes in the bilateral lung fields.
hematocrit 24%, total leukocyte count 19.7 109/l (neutrophils 67%, including band forms with toxic granulations, lymphocytes 32%), platelets 233 109/l. The erythrocyte sedimentation rate was 84 mm (first hour) and C-reactive protein was 142 mg/l (normal <6 mg/l). She was started on antibacterial chemotherapy with intravenous ampicillin and netilmicin, pending blood cultures. A Giemsa-stained peripheral blood smear showed trophozoites of Plasmodium falciparum, with parasitemia quantitatively reported as 20–50 parasites per 100 fields. The antigen test (optiMAL) for P. falciparum was positive, while that for P. vivax was negative. The peripheral blood smear of the mother at presentation failed to reveal malarial parasites and the antigen tests were negative. She and her husband both had negative ELISA for HIV-I and II. The blood urea nitrogen was 48 mg/dl, creatinine 2.4 mg/dl, total bilirubin 3.7 mg/dl with direct reacting fraction of 1.2 mg/dl, alanine aminotransferase 172 IU/l, aspartate aminotransferase 124 IU/l, and alkaline phosphatase 140 U/l (normal <120 IU/l). A chest radiograph obtained concurrently showed diffuse miliary mottling of bilateral lung fields (Figure 1). In view of her critical condition, as per the recommendations of the Indian Academy of Paediatrics,2 she was started on intravenous artesunate (loading dose of 2.4 mg/kg, followed by 1.2 mg/kg at 12 and 24 hours, then 1.2 mg/kg daily for 6 days), which was followed by oral mefloquine at 25 mg/kg divided into two doses (15 mg/kg and 10 mg/kg at 6hourly interval). Cultures of the blood and urine were sterile. The suggestive chest radiograph prompted an additional search for pulmonary tuberculosis. The early morning gastric aspirates were graded as 2+ (1–10 AFB per field in at least 50 fields examined) as per the guidelines of the IUATLD1 on days 1, 2, and 3. A lumbar puncture cerebrospinal fluid (CSF) examination revealed the following: normal opening pressure, glucose 24 mg/dl, protein 78 mg/dl, no AFB on smear stain. The blood BACTEC culture was positive for Mycobacterium tuberculosis on the 18th day, while the
The criteria for the diagnosis of true congenital tuberculosis were established by Beitzke in 1935.3 The criteria require that the neonates have proved tuberculous lesions and one of the following: lesions in the first few days of life, a primary hepatic complex, or the exclusion of postnatal transmission by the separation of the infant at birth from the mother and other sources of infection. The criteria proposed by Beitzke were based on the demonstration of primary hepatic complex or caseating hepatic granulomas on autopsy specimens. Increasing survival of the congenitally infected infants has made the application of the mentioned criteria difficult in current practice. Cantwell et al.4 proposed a revision in 1994, which is the accepted standard in diagnosing congenital tuberculosis worldwide today, and includes proven tuberculous lesions in the neonate and at least one of the following: (1) lesions in the first week of life; (2) a primary hepatic complex or caseating hepatic granulomas; (3) tuberculous infection of the placenta or the maternal genital tract; and (4) exclusion of the possibility of postnatal transmission by a thorough investigation of contacts. Cases of tuberculosis presenting shortly after birth comprise both the true congenital forms and those acquired postnatally.5 The postnatal type is significantly more common than the true congenital type. This may be due to shortcomings in the diagnostic and surveillance systems, especially in developing countries. The distinction between the true congenital cases and those acquired postnatally is purely of epidemiological significance because the modes of presentation, treatment, and immediate prognosis do not differ between the two groups and may be difficult to differentiate at times. Hence, the term ‘perinatal tuberculosis’ may be more appropriate for the tuberculous disease acquired before, during, or immediately after birth.5,6 The presently reported child qualifies as a case of perinatal tuberculosis because of the failure to meet the Cantwell criteria. Moreover, the father was the most likely source of the infection. Malaria is responsible for more than 300 000 fetal and infant deaths and 2500 deaths of pregnant women worldwide each year.7 Malaria in pregnancy can result in premature delivery, intrauterine growth retardation, perinatal mortality, anemia, abortion, low birth weight, and maternal deaths.8,9 Occasionally, perinatal malaria infection may cause cord parasitemia, early and late neonatal malaria. Placental infection with malarial parasites may result in their transplacental transmission, although the infant born may remain asymptomatic and healthy.10 There is lack of consensus on the definition of congenital malaria. Traditionally, in endemic countries, congenital malaria is diagnosed when the parasite is seen on the infant’s peripheral blood smear during the first week of life.11 Although we were unable to demonstrate malarial parasites in the maternal peripheral circulation with routine microscopy at the time of presentation, the diagnosis of congenital malaria in our patient at age 34 days was established by the presence of P. falciparum on the peripheral smear, with a negative history of vector exposure
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R. Thapa et al. / International Journal of Infectious Diseases 14 (2010) e254–e256
postnatally. There was no previous documentation of malarial infection in the mother apart from the one during her eighth month of gestation. The natural immune suppression that is characteristic of pregnancy might have been responsible for the episode of P. falciparum during her gestation.12 The episode was treated inadequately with chloroquine, which supports our assumption that the malaria in the infant was indeed congenital. Newborns presenting with malaria and tuberculosis may not be unusual in India, which remains endemic for both the diseases. Furthermore, plasmodia infections in humans are associated with partial immune suppression. The relatively immature immune system characteristic of the neonatal period and the partial immunosuppression due to the malarial infection most likely provided an ideal setting for the development of the tuberculous infection, especially in the presence of an open case of PTB in the family. In the present instance, PTB in the father coupled with the suggestive signs on the infant’s chest radiograph prompted a search for an underlying tuberculous infection, despite the presence of congenital malaria. To our knowledge, there are no reports on the co-occurrence of perinatal malaria and tuberculosis in the existing literature. It may be possible that many such cases in India are missed because of the lack of proper diagnostic facilities in the rural provinces where the burden of such diseases is particularly high. However, it is prudent to bear in mind that there may, at times, be more than one etiology in newborns presenting with ‘suspected’ sepsis. Thorough evaluation of the newborn and the close contacts may result in delineation of multiple causes for the presenting symptoms.
Conflict of interest No conflict of interest to declare. References 1. Enarson DA, Reider HL, Arnadottir T, Trebucq A. Management of tuberculosis: a guide for low income countries. IUATLD; 2000. Available at: http://www.iuatld. org/pdf/en/guides_publications/management_of_tb.pdf.(accessed June 2009). 2. Kundu R, Ganguly N, Ghosh TK, Choudhury P, Saha RC. Diagnosis and management of malaria in children: recommendations and IAP plan of action. Indian Pediatr 2005;42:1101–14. 3. Beitzke H. Uber die angioborene tuberkulose infection. Ergeebn Tuberk Forsch 1935;7:1–30. 4. Cantwell MF, Shehab ZM, Costello AM, Sands L, Green WF, Ewing Jr EP, et al. Brief report: congenital tuberculosis. N Engl J Med 1994;330:1051–4. 5. Singh M, Kothur K, Dayal D, Kusuma S. Perinatal tuberculosis: a case series. J Trop Pediatr 2006;53:135–8. 6. Pillay T, Khan M, Moodley J, Adhikari M, Coovadia H. Perinatal tuberculosis and HIV-I: considerations for resource-limited settings. Lancet Infect Dis 2004;4: 155–65. 7. Steketee RW, Nahlen BL, Parise ME, Menendez C. The burden of malaria in pregnancy in malaria-endemic areas. Am J Trop Med Hyg 2001;64:28–35. 8. Brabin BJ. An assessment of low birth weight risk in primiparae as an indicator of malaria control in pregnancy. Int J Epidemiol 1991;20:276–83. 9. Menendez C. Malaria during pregnancy: priority area of malaria research and control. Parasitol Today 1995;11:178–83. 10. Redd SC, Wirima JJ, Steketee RW, Breman JG, Heymann DL. Transplacental transmission of Plasmodium falciparum in rural Malawi. Am J Trop Med Hyg 1996;55:57–60. 11. Laosombat V, Dharmasakti S. Neonatal malaria in southern Thailand. Southeast Asian J Trop Med Public Health 1981;12:99–103. 12. Meyer MC, Barron DN, Clements RC. Immigrant medicine, part I: evaluation, diagnosis, and treatment of commonly encountered diseases. Emerg Med Rep 2003;24:31–49.
Contents lists available at ScienceDirect
International Journal of Infectious Diseases journal homepage: www.elsevier.com/locate/ijid
Case Report
Perinatal malaria and tuberculosis co-infection: A case report Rajoo Thapa *, Debkrishna Mallick, Biswajit Biswas The Department of Pediatrics and Division of Neonatology, The Institute of Child Health, 11, Dr. Biresh Guha Street, Kolkata-700017, West Bengal, India
A R T I C L E I N F O
A B S T R A C T
Article history: Received 31 August 2008 Received in revised form 9 April 2009 Accepted 17 April 2009
India remains endemic for both vivax malaria and tuberculosis. In spite of the high burden of tuberculosis in the country, reports on congenital tuberculosis in the literature are limited. We report herein an unusual instance of co-occurrence of perinatal falciparum malaria and tuberculosis in a 34day-old female newborn, who presented with symptoms of sepsis. The diagnosis was based on the demonstration of Plasmodium falciparum on peripheral blood smear and tubercle bacilli in gastric aspirate samples. The maternal history for falciparum malaria was positive during her eighth month of pregnancy and the father was an open case of sputum smear-positive pulmonary tuberculosis. She responded dramatically to combined antimalarial and antitubercular chemotherapy. A search for combined etiologies in presumed ‘sepsis’ in the newborn, guided by history, physical examination, and laboratory investigations, is warranted. ß 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Corresponding Editor: William Cameron, Ottawa, Canada Keywords: Perinatal falciparum malaria Perinatal tuberculosis Sepsis Antimalarial chemotherapy Antitubercular chemotherapy
1. Introduction Both congenital tuberculosis and congenital malaria are rarely diagnosed, even in countries endemic for the adult forms of the diseases. The presentation is usually with non-specific signs and symptoms. A meticulous past medical history, including that of the maternal gestation and family members is often the initial suspicion-arousing event. Both the diseases are associated with extremely high mortality in the absence of timely recognition and prompt therapy. We report an unusual case of a 34-day-old female newborn with co-occurrence of perinatal falciparum malaria and tuberculosis, suspected primarily on the basis of positive maternal and family history. She responded dramatically to combined antimalarial and antitubercular therapy. 2. Case report A 34-day-old, term, female infant, born to non-consanguineous parents was initially seen for a three-day history of cough and progressive lethargy, with poor breastfeeding and fever. The mother also noted that the baby had turned progressively paler over the last week. There was no history of abdominal distension, oliguria, alteration of consciousness, convulsions, or prolonged jaundice in the neonatal period. She was delivered at home by a traditional birth attendant, by spontaneous vaginal delivery, and
* Corresponding author. Tel.: +91 33 22905686; fax: +91 33 22475686. E-mail address: [email protected] (R. Thapa).
there had been no immediate postnatal complications. She was not immunized at birth. The mother’s past medical history was significant for an episode of fever due to falciparum malaria at eight months of gestation, which had been treated with chloroquine, but unfortunately not as per the recommendations of the National Malaria Eradication Programme, Department of Health and Family Welfare, Government of India. Besides this, she denied any other illnesses during her gestation or in the immediate past. The father was an open case of sputum smear-positive pulmonary tuberculosis (PTB) with a suggestive chest radiograph, diagnosed a month previously and was on intensive phase antitubercular chemotherapy (isoniazid, rifampin, pyrazinamide, and ethambutol) with partial response. At the time of the baby’s admission, the father’s sputum remained positive for acid-fast bacilli (AFB; graded as 1+ (10–99 AFB per 100 fields examined) as per the guidelines of the International Union Against Tuberculosis and Lung Disease (IUATLD)1). On examination, the infant appeared pale, dehydrated, and tachypneic with labored breathing. She weighed 2.5 kg and measured 53 cm in length (both below the third percentile for age and sex). The rectal temperature was 39 8C, and she had a heart rate of 194 per minute, a respiratory rate of 86 per minute, and an oxygen saturation of 87% in room air. Moderate intercostal, suprasternal, and subcostal chest retractions were noted. The chest auscultation revealed bilateral, diffuse crepitations with occasional rales. The liver and the spleen were palpable 3.5 cm and 3 cm below the right and the left costal margins, respectively. Examination of the other major systems was non-contributory. A complete hemogram showed the following: hemoglobin 6.2 g/dl,
1201-9712/$36.00 – see front matter ß 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ijid.2009.04.005
R. Thapa et al. / International Journal of Infectious Diseases 14 (2010) e254–e256
e255
same for CSF was negative. The mother did not consent to invasive diagnostic procedures for the exclusion of genitourinary tuberculosis; however her urine sample cultures for AFB on two occasions were negative. She was started on a four-drug regimen comprising isoniazid, rifampin, pyrazinamide, and streptomycin, at the recommended doses. The infant improved dramatically on combined antimalarial and antitubercular therapy. At 12 weeks of follow-up, she showed remarkable weight gain and was developing normally with age-appropriate anthropometry. At the time of writing, she was on chemotherapy with two drugs, isoniazid and rifampin. 3. Discussion
Figure 1. Chest radiograph of the newborn showing diffuse miliary changes in the bilateral lung fields.
hematocrit 24%, total leukocyte count 19.7 109/l (neutrophils 67%, including band forms with toxic granulations, lymphocytes 32%), platelets 233 109/l. The erythrocyte sedimentation rate was 84 mm (first hour) and C-reactive protein was 142 mg/l (normal <6 mg/l). She was started on antibacterial chemotherapy with intravenous ampicillin and netilmicin, pending blood cultures. A Giemsa-stained peripheral blood smear showed trophozoites of Plasmodium falciparum, with parasitemia quantitatively reported as 20–50 parasites per 100 fields. The antigen test (optiMAL) for P. falciparum was positive, while that for P. vivax was negative. The peripheral blood smear of the mother at presentation failed to reveal malarial parasites and the antigen tests were negative. She and her husband both had negative ELISA for HIV-I and II. The blood urea nitrogen was 48 mg/dl, creatinine 2.4 mg/dl, total bilirubin 3.7 mg/dl with direct reacting fraction of 1.2 mg/dl, alanine aminotransferase 172 IU/l, aspartate aminotransferase 124 IU/l, and alkaline phosphatase 140 U/l (normal <120 IU/l). A chest radiograph obtained concurrently showed diffuse miliary mottling of bilateral lung fields (Figure 1). In view of her critical condition, as per the recommendations of the Indian Academy of Paediatrics,2 she was started on intravenous artesunate (loading dose of 2.4 mg/kg, followed by 1.2 mg/kg at 12 and 24 hours, then 1.2 mg/kg daily for 6 days), which was followed by oral mefloquine at 25 mg/kg divided into two doses (15 mg/kg and 10 mg/kg at 6hourly interval). Cultures of the blood and urine were sterile. The suggestive chest radiograph prompted an additional search for pulmonary tuberculosis. The early morning gastric aspirates were graded as 2+ (1–10 AFB per field in at least 50 fields examined) as per the guidelines of the IUATLD1 on days 1, 2, and 3. A lumbar puncture cerebrospinal fluid (CSF) examination revealed the following: normal opening pressure, glucose 24 mg/dl, protein 78 mg/dl, no AFB on smear stain. The blood BACTEC culture was positive for Mycobacterium tuberculosis on the 18th day, while the
The criteria for the diagnosis of true congenital tuberculosis were established by Beitzke in 1935.3 The criteria require that the neonates have proved tuberculous lesions and one of the following: lesions in the first few days of life, a primary hepatic complex, or the exclusion of postnatal transmission by the separation of the infant at birth from the mother and other sources of infection. The criteria proposed by Beitzke were based on the demonstration of primary hepatic complex or caseating hepatic granulomas on autopsy specimens. Increasing survival of the congenitally infected infants has made the application of the mentioned criteria difficult in current practice. Cantwell et al.4 proposed a revision in 1994, which is the accepted standard in diagnosing congenital tuberculosis worldwide today, and includes proven tuberculous lesions in the neonate and at least one of the following: (1) lesions in the first week of life; (2) a primary hepatic complex or caseating hepatic granulomas; (3) tuberculous infection of the placenta or the maternal genital tract; and (4) exclusion of the possibility of postnatal transmission by a thorough investigation of contacts. Cases of tuberculosis presenting shortly after birth comprise both the true congenital forms and those acquired postnatally.5 The postnatal type is significantly more common than the true congenital type. This may be due to shortcomings in the diagnostic and surveillance systems, especially in developing countries. The distinction between the true congenital cases and those acquired postnatally is purely of epidemiological significance because the modes of presentation, treatment, and immediate prognosis do not differ between the two groups and may be difficult to differentiate at times. Hence, the term ‘perinatal tuberculosis’ may be more appropriate for the tuberculous disease acquired before, during, or immediately after birth.5,6 The presently reported child qualifies as a case of perinatal tuberculosis because of the failure to meet the Cantwell criteria. Moreover, the father was the most likely source of the infection. Malaria is responsible for more than 300 000 fetal and infant deaths and 2500 deaths of pregnant women worldwide each year.7 Malaria in pregnancy can result in premature delivery, intrauterine growth retardation, perinatal mortality, anemia, abortion, low birth weight, and maternal deaths.8,9 Occasionally, perinatal malaria infection may cause cord parasitemia, early and late neonatal malaria. Placental infection with malarial parasites may result in their transplacental transmission, although the infant born may remain asymptomatic and healthy.10 There is lack of consensus on the definition of congenital malaria. Traditionally, in endemic countries, congenital malaria is diagnosed when the parasite is seen on the infant’s peripheral blood smear during the first week of life.11 Although we were unable to demonstrate malarial parasites in the maternal peripheral circulation with routine microscopy at the time of presentation, the diagnosis of congenital malaria in our patient at age 34 days was established by the presence of P. falciparum on the peripheral smear, with a negative history of vector exposure
e256
R. Thapa et al. / International Journal of Infectious Diseases 14 (2010) e254–e256
postnatally. There was no previous documentation of malarial infection in the mother apart from the one during her eighth month of gestation. The natural immune suppression that is characteristic of pregnancy might have been responsible for the episode of P. falciparum during her gestation.12 The episode was treated inadequately with chloroquine, which supports our assumption that the malaria in the infant was indeed congenital. Newborns presenting with malaria and tuberculosis may not be unusual in India, which remains endemic for both the diseases. Furthermore, plasmodia infections in humans are associated with partial immune suppression. The relatively immature immune system characteristic of the neonatal period and the partial immunosuppression due to the malarial infection most likely provided an ideal setting for the development of the tuberculous infection, especially in the presence of an open case of PTB in the family. In the present instance, PTB in the father coupled with the suggestive signs on the infant’s chest radiograph prompted a search for an underlying tuberculous infection, despite the presence of congenital malaria. To our knowledge, there are no reports on the co-occurrence of perinatal malaria and tuberculosis in the existing literature. It may be possible that many such cases in India are missed because of the lack of proper diagnostic facilities in the rural provinces where the burden of such diseases is particularly high. However, it is prudent to bear in mind that there may, at times, be more than one etiology in newborns presenting with ‘suspected’ sepsis. Thorough evaluation of the newborn and the close contacts may result in delineation of multiple causes for the presenting symptoms.
Conflict of interest No conflict of interest to declare. References 1. Enarson DA, Reider HL, Arnadottir T, Trebucq A. Management of tuberculosis: a guide for low income countries. IUATLD; 2000. Available at: http://www.iuatld. org/pdf/en/guides_publications/management_of_tb.pdf.(accessed June 2009). 2. Kundu R, Ganguly N, Ghosh TK, Choudhury P, Saha RC. Diagnosis and management of malaria in children: recommendations and IAP plan of action. Indian Pediatr 2005;42:1101–14. 3. Beitzke H. Uber die angioborene tuberkulose infection. Ergeebn Tuberk Forsch 1935;7:1–30. 4. Cantwell MF, Shehab ZM, Costello AM, Sands L, Green WF, Ewing Jr EP, et al. Brief report: congenital tuberculosis. N Engl J Med 1994;330:1051–4. 5. Singh M, Kothur K, Dayal D, Kusuma S. Perinatal tuberculosis: a case series. J Trop Pediatr 2006;53:135–8. 6. Pillay T, Khan M, Moodley J, Adhikari M, Coovadia H. Perinatal tuberculosis and HIV-I: considerations for resource-limited settings. Lancet Infect Dis 2004;4: 155–65. 7. Steketee RW, Nahlen BL, Parise ME, Menendez C. The burden of malaria in pregnancy in malaria-endemic areas. Am J Trop Med Hyg 2001;64:28–35. 8. Brabin BJ. An assessment of low birth weight risk in primiparae as an indicator of malaria control in pregnancy. Int J Epidemiol 1991;20:276–83. 9. Menendez C. Malaria during pregnancy: priority area of malaria research and control. Parasitol Today 1995;11:178–83. 10. Redd SC, Wirima JJ, Steketee RW, Breman JG, Heymann DL. Transplacental transmission of Plasmodium falciparum in rural Malawi. Am J Trop Med Hyg 1996;55:57–60. 11. Laosombat V, Dharmasakti S. Neonatal malaria in southern Thailand. Southeast Asian J Trop Med Public Health 1981;12:99–103. 12. Meyer MC, Barron DN, Clements RC. Immigrant medicine, part I: evaluation, diagnosis, and treatment of commonly encountered diseases. Emerg Med Rep 2003;24:31–49.