Bernhard Nocht Institute for Tropical Medicine

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Bernhard Nocht Institute for Tropical Medicine

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Bernhard Nocht Institute for Tropical Medicine (Bernhard-Nocht-Institut für Tropenmedizin) (BNITM) in Hamburg is Germany's largest institution for tropical medicine, with a workforce of about 250 people in Hamburg. It is member of the Leibniz-Association.

Bernhard Nocht Institute

History[edit]

The cholera epidemic of the year 1892 claimed thousands of lives and prompted the Senate and Parliament of the City of Hamburg to reform the health care system. The Tropical Medicine Institute was founded with the support of the Imperial Government to research ship and tropical diseases and to train ship and colonial physicians. In 1893, the naval physician Bernhard Nocht [de] was introduced to the newly created position of port physician. For the medical care of seamen suffering from internal diseases, he was also given a department in the St. Georg General Hospital. Contrary to the plans of the bacteriologist Robert Koch, Nocht established Hamburg in 1899 as the location for an institute for the research of tropical diseases, since "due to overseas traffic there are many people with treatment needs at this point". On 1 October 1900 the "Institute for Maritime and Tropical Diseases" with 24 employees was opened in the former administration building of the naval hospital at Hamburg's Landungsbrücken. Since 2006, the inpatient care has taken place at the University Medical Center Hamburg-Eppendorf.

Building[edit]

Between 1910 and 1914, the three-part clinker building with laboratory wing, hospital and animal house was built according to plans by Fritz Schumacher. The building wing is located in the St. Pauli district between Bernhard Nocht Street on the high north side and the slope of Davidstreet [de] leading down to the harbor shore. After 1945 the building, damaged by bombs, was re-built. From 2003 a new wing was built on the site of the former animal house, which was put into operation at the end of January 2008. In particular, the high-security laboratories were completely redesigned and have since then been among the safest in the world (biosafety level 4). The numerous decorative reliefs on the façade of the old building were created by the artist Johann Michael Bossard [de]. The buildings of the Regional Centre of the German Weather Service and the Federal Maritime and Hydrographic Agency are located in the course of the road to the east.

Research[edit]

The institute is divided into three research sections:[1] the Molecular Biology and Immunology Division, the Clinical Research Division and the Epidemiology and Diagnostics Division. The National Reference Centre for Tropical Pathogens is also located at BNITM. Until the end of 2007, the Bernhard Nocht Institute was supported by the Federal Ministry of Health and the Ministry of Social Affairs, Family, Health and Consumer Protection of the Free and Hanseatic City of Hamburg. On 1 January 2008, the BNITM merged into the Leibniz Association.

The Institute's current scientific focus is on malaria, haemorrhagic fever viruses (Lassa, Marburg, Ebola and Crimean Congo Virus), on immunology, epidemiology and clinical studies of tropical infections as well as on the mechanisms of the viral transmission by mosquitoes. For the handling of highly pathogenic viruses and infected insects, the Institute has laboratories of the highest biosafety level (BSL-4) and a BSL-3 insectary. The BNITM comprises the National Reference Centre for the detection of all tropical pathogens and the WHO Collaborating Centre for arboviruses and haemorrhagic fever viruses.

Recent successes of the institute include the identification and development of a test for the SARS pathogen (Christian Drosten, Stephan Günther [de] 2003), the development of new therapeutic approaches against nematodes, especially in river blindness (Achim Hörauf 1998), on bacteria living symbiotically with the worms, and the clarification of a still missing transitional stage of the malaria pathogen (Merosome, Volker Heussler [de] 2006). The couple Paul Racz [de] and Klara Tenner-Racz from the Institute's Pathology Department is also known for their achievements in AIDS research.

Research contributions[edit]

The following list contains a few of the contributions made at the Bernhard Nocht Institute:[2]

Directors[edit]

Since 2008, the institute has been headed by a board of trustees. It consists of three scientists and the commercial director. The first chairman of the board was the physician Rolf Horstmann, who had headed the Department of Tropical Medicine Basic Research at the BNITM since 1998. Bernhard Fleischer was deputy chairman. The third member of the board was Egbert Tannich. In early 2018, Egbert Tannich took up his position as Chairman of the Institute's Board of Directors. In addition to managing director Birgit Müller, Jürgen May and Stephan Günther joined the board. The research groups also underwent restructuring: Egbert Tannich took over the establishment of the "Infection Diagnostics" department. Michael Ramharter was appointed to the W3 professorship "Clinical Tropical Medicine" at the University Hospital Hamburg-Eppendorf and moved to the BNITM with his department "Clinical Research".

Other[edit]

Today, the research priorities are divided between the Robert Koch Institute (RKI) and the BNITM. While the BNITM is responsible for research abroad, the RKI is responsible for issues on research and hygiene within Germany

A branch office of the Institute was located in the hospital of the German mining settlement of Bong Town in the West African state of Liberia, which was closed in the 1990s as a result of the civil war.

On 23 February 2015, Health Minister Hermann Gröhe visited the BNITM.

As a member of the scientific community Gottfried Wilhelm Leibniz (Wissenschaftsgemeinschaft WGL), the Institute is institutionally funded by the Federal Government and the Federal States as a "research institute of supra-regional importance".

Among the population the BNITM is also known as "The Tropical Institute" or is sometimes colloquially referred to as "Tropical Hospital".

The German Armed Forces Hospital Hamburg closely cooperates with the BNITM, so that, i.a the Tropical Medicine Department of the German Armed Forces Hospital has been accommodated in the BNITM since 2005.

Since 2006 there is no more hospital operation at the BNITM. The Bernhard Nocht Medal for Tropical Medicine is awarded by the Bernhard Nocht Institute and the German Society for Tropical Medicine and Global Health; the winner gives a lecture in Hamburg. Some of the prize winners, such as Walter Kikuth [de] and Hans Vogel, also did research at the Bernhard Nocht Institute.

At the end of January 2020, Chairman Tannich attracted considerable public attention in Germany when he characterized, on one of the major national TV channels (ARD), coronavirus SARS-CoV2 as object of a media hype: "We are surprised at what lengths there is now media coverage, at its intensity, and how much space is assigned to it. We are astonished how often it is repeated again and again."[5] Tannich emphasized "that the danger posed by the virus [SARS-CoV2] is significantly smaller than some thought at the beginning."[6]

Literature[edit]

See also[edit]

References[edit]

Further reading[edit]


2000 (September) - "100 years of tropical medicine in Hamburg at the Bernhard Nocht Institute", written by Bernhard Fleischer 

Saved PDF : [HP00D7][GDrive] 

Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 95, Suppl. I: 17-23, 2000 

The Bernhard Nocht Institute (BNI) is a four months younger and much smaller sibling of the Instituto Oswaldo Cruz. It was founded on 1 October 1900 as an Institut für Schiffs- und Tropenkrankheiten (Institute for Maritime and Tropical Diseases) and was later named after its founder and first director Bernhard Nocht. Today it is the Germany’s largest institution for research in tropical medicine. It is a government institution affiliated to the Federal Ministry of Health of Germany and the Department of Health of the State of Hamburg. As the center for research in tropical medicine in Germany the BNI is dedicated to research, training and patient care in the area of human infectious diseases, which are of particular relevance in the tropics. It is the primary mission of the BNI to develop means to the control of these diseases. Secondary missions are to provide expertise for regional and national authorities and to directly and indirectly improve the health care for national and regional citizens in regard to diseases of the tropics. Key words: Bernhard Nocht Institute - tropical medicine - research

Memórias do Instituto Oswaldo Cruz (Portuguese for "Memoirs of the Oswaldo Cruz Institute") is a peer-reviewed open access medical journal covering parasitology, microbiology, and tropical medicine. It was established in 1909 by the Brazilian physician Oswaldo Cruz and is published by the Oswaldo Cruz Foundation (FIOCRUZ) eight times a year. The editor-in-chief is Adeilton Brandão (IOC/FIOCRUZ).[1]

Image of page 17 : [HP00D8][GDrive] 
Image of page 18 : [HP00D9][GDrive] 
Image of page 19 : [HP00DA][GDrive] 

PAST

The roots of the Bernhard Nocht Institute (BNI)

lie in the great cholera outbreak in Hamburg in

1892 during its fifth pandemic. Bernhard Nocht

(1957-1945), a young Navy Doctor who had been

trained at Robert Koch’s Institut in Berlin, came

to Hamburg to help Koch to bring the epidemic

under control. Because of his ability, it was subsequently

offered him the position of a Harbour Doctor

and he was appointed in 1893.

In this office Nocht saw the great and increasing

number of sailors and travelers with tropical

diseases entering Hamburg by ship. In the year

1900, for example, 500 ships with 15,000 persons

arrived from overseas in the port of Hamburg.

Tropical and other infections such as typhus, dysenteries

or tuberculosis were commonly seen. For

example, 11% of the travelers that arrived on

sailing ships had malaria and 6% of travelers

from steam ships.

From a previous visit to the tropics, Nocht had

experience with tropical diseases and tried to persuade

the authorities of the need to establish an

Institute for research, training and therapy of tropical

infections.

Although Robert Koch tried to bring such an

Institute to Berlin at Nocht’s instigation, an Institut

für Schiffs-und Tropenkrankheiten (Institute for

Maritime and Tropical Diseases) was founded in

Hamburg on 1 October 1900. Nocht was the first

director, acting from 1900 to 1930. Within a short

time he was able to gather a group of ambitious

and able scientists (Fig. 1). Fritz Schaudinn, who

discovered Treponema pallidum, was the first head

of the Department of Protozoology. After his sudden

death in 1906, Stanislaus von Prowazek was

his successor. Gustav Giemsa, the inventor of the

famous Giemsa stain, started to work in 1900 as

head of the Department of Chemistry. Friedrich

Fülleborn, later Nocht’s successor as director, was

the first head of the Department of Helminthology.

In 1914, the Institute had, besides the director,

six scientists on its own payroll and four scientists

were financed by the army or the colonial office.

In this year the Institute moved into a new building

that still today accomodates it (Fig. 2). The costs

of the building were 1,500,000 marks and of the

interior 800,000 marks. The annual budget for research

of the Institute in 1914 was 246,302 marks.

In the first decades of the BNI a number of

major discoveries was made. Milestones were the

discovery of Rickettsia prowazecki, the agent of

epidemic typhus, by von Prowazeck and da Rocha-

Lima. Both von Prowazeck and da Rocha-Lima

got infected with the agent during their work and

von Prowazeck died in 1915. Da Rocha-Lima

named the agent after his colleague and friend. He

later described another louse-transmitted infectious

agent, Rochalimea (now Bartonella) quintana, the

causing agent of trench fever. Von Prowazek also

described for the first time the infectious origin of

trachoma (Halberstaedter & Prowazek 1909). As

an animal model for the chemotherapy of malaria,

the avian malaria was established and found suitable

to test new derivatives of chinin such as

plasmochin and atebrin. Using this model the protozoologist

Eduard Reichenow and his coworkers

described the extraerythrocytic development of

plasmodial sporozoites as the missing link between

the infective sporozoite and the infected erythrocyte

(Reichenow & Mudrow 1943).

The helminthologist Hans Vogel discovered in

1931 the developmental cycle of Opisthorchis

felineus (Vogel 1934) and described later in experiments

lasting from 1938 to 1950, for the first

time immunity against a trematode infection (Vogel

& Minning 1953). In the 50’s, Vogel (1955) discovered

Echinococcus multilocularis as a new species.

More recent findings include the demonstration

by Paul Racz and Klara Tenner-Racz together

with Ashley Haase (Minneapolis) of a massive multiplication

of HIV in the lymphnodes in the incubation

period of Aids. Egbert Tannich was able in

1989 to separate Entamoeba histolytica and E.

dispar (Tannich et al. 1989).

Nearly from its beginning the BNI had connections

with the Instituto Oswaldo Cruz. Gustav

Giemsa and Stanislaus von Prowazek stayed upon

invitation by the Brazilian Government in 1908 in

the Instituto Oswaldo Cruz (Fig. 3). In fact Giemsa

was an author of the very first paper published by

the Memórias do Instituto Oswaldo Cruz (Giemsa

& Godoy 1909). In September 1909, Nocht appointed

Henrique da Rocha-Lima, who had been

previously Head of the Department of Pathology

at Instituto Oswaldo Cruz, as Head of a new Department

of Pathology in his Institute. da Rocha-

Lima stayed until December 1927 in Hamburg.

Nocht himself came in 1929 to visit the Instituto

Oswaldo Cruz. In 1977, the Department of Electron

Microscopy of the Instituto Oswaldo Cruz was

established jointly with the BNI. Fig. 4 shows the

head of BNI’s Department of Protozoology, Prof.

Heinz Mühlpfordt, demonstrating the use of the

microscope to the President of Brazil Ernesto

Geisel.

PRESENT

One hundred years later, the BNI is still the

Germany’s largest research institute for tropical

medicine. Research at the BNI is devoted to the

characterization of host-pathogen-interactions in

tropical infectious diseases. The research activities

of the BNI concentrate on three areas: (1) cellular

and molecular biology of infectious agents

that cause tropical diseases; (2) the host response

to such agents and its role in protection and pathology;

(3) a disease oriented approach to pathogenesis

and pathology. Accordingly BNI’s work

focuses on infectious diseases caused by parasites

and tropical viruses. Main topics of work are pathogenicity

factors of parasites and cell biology of

parasites, the analysis of the host-parasite-relationship

including immunological defense mechanisms,

and definition of genes causing susceptibility

to certain tropical infections. In all these ventures

special emphasis is put on two issues: relevance

for disease prevention and control, and use

of tropical infections as models for general issues

in medicine and biology.

The BNI is a government institution affiliated

to the Federal Ministry of Health of the Federal

Republic of Germany and the Ministry of Health

of the State of Hamburg and is financed jointly by

the Federal Government and the States of the Federal

Republic of Germany. The BNI has many cooperations

and contacts with developing countries,

most of them with countries in Africa but also with

countries in South America and Asia. The Institute

maintains a Cooperative Research Center in

Kumasi, Ghana, mainly for research on onchocerciasis

and malaria. The cooperative center is established

according to a state agreement between

the Republic of Ghana and the State of Hamburg,

to establish longstanding contacts to scientists of

the host country. Its hallmark is that each research

project is carried out jointly by scientists from Hamburg

and from Kumasi. Projects on Lassa fever and

amoebiasis are presently pursued in Guinea and

Vietnam, respectively.

Besides research, the BNI has many educational

and service activities in the area of tropical medicine.

Three members of the BNI hold full professorships

at the University of Hamburg and are engaged

in teaching. A three-month’s course on tropical

medicine is held each year and is approved as

an officially accredited diploma course by the

American Society of Tropical Medicine and Hygiene.

The BNI includes a Department of Clinical

Medicine with 68 beds and an outpatient clinic

where patients with tropical diseases are treated.

The BNI performs specialized diagnostic tests for

the detection of pathogens causing parasitic diseases.

The Institute is equipped with the only true


BSL4 laboratory in Germany for work with hemorrhagic

fever viruses.

To fulfill its aims the BNI has a specific organizational

structure. It is composed of three scientific

sections (Parasitology, Medical Microbiology,

Tropical Medicine) containing departments established

for longer periods of time and temporary

research groups. These research groups are installed

for a limited period of time only and will be

replaced by new groups according to scientific

necessity. The Parasitology Section contains the

Department of Molecular Parasitology and several

research groups working on pathogenicity factors,

biology of pathogens including biochemical pathways

and mechanisms of adaptation and evasion.

The Medical Microbiology Section contains the

Departments of Immunology and Virology, research

groups working on host-responses to filariae

or to viruses, a Central Diagnostic Unit developing

new diagnostic tools and the animal experimentation

facilities. The Tropical Medicine Section

contains the Departments of Molecular Medicine,

Pathology, and Clinical Chemistry. The Department

of Molecular Medicine runs the Kumasi

Centre for Collaborative Research in Tropical

Medicine in Kumasi, Ghana. The presence of a

Clinical Department performing diagnosis and

treatment of patients provides a distinctive advantage

to the BNI. It is a valuable addition to the clinical

research performed in the tropics because patients

seen in Hamburg have usually primary infections

with only one infecting agent, and intensive

research applying high technology and follow-

up studies for longer periods of time are possible

in Hamburg.

SPECIFIC RESEARCH PROGRAMS

Amoebiasis research is a major research program

in which scientists from several sections work

together. This program covers a variety of aspects

concerning the biology and pathogenicity of E.

histolytica. In 1989, the group of Egbert Tannich

had first described that pathogenic and non-pathogenic

amoebae could be distinguished by molecular

genetic methods (Tannich et al. 1989). In fact,

the two species E. histolytica and E. dispar are as

distant in evolution as mice and rats. Subsequently,

the molecules serving as pathogenicity factors have

been determined (Bruchhaus et al. 1996, Tannich

1998), among the cysteine proteins, the large 170

kD galactose specific surface lectin and the

amoebapores, highly efficient and conserved poreforming

proteins. Transfixion and stable expression

of heterologous genes is now possible in E.

histolytica and E. dispar allowing elucidating the

role of various gene products in pathogenesis

(Hamann et al. 1995). In vitro diagnostic tests have

been developed to discriminate infection by pathogenic

amoebae from infection by non-pathogenic

amoebae. A possible candidate antigen for a vaccine

has been identified (Lotter et al. 1997).

Filariasis research is the second major program

of the BNI since the 60’s. The main topic is onchocerciasis

(river blindness) caused by the filaria,

Onchocerca volvulus. Work on lymphatic filariasis

especially on biochemical pathways possibly

exploitable for the design of new antifilarial drugs,

is also performed.

Adult O. volvulus worms developed from infective

larval stages live in subcutaneous nodules

from where they release microfilariae (MF) which

migrate in the skin. The departments of Helminthology,

Entomology, Molecular Genetics and Immunology

cooperate in the definition of O. volvulus

proteins and in the immunological effector

mechanisms involved in anti-parasitic defense. The

vectors transmitting infective larvae are studied and

the differential susceptibility of exposed individuals

which can be grouped into (i) patients with generalized

disease, showing a high load of worms

and MF accompanied by immunological tolerance

against onchocercal antigens; (ii) patients with low

MF load and immune reactivity leading to severe

dermatitis; and (iii) putatively immune individuals

that remain free of worms despite exposure to

infective larvae. These forms of reactivity are associated

with certain HLA class II antigens (Meyer

et al. 1994). T cells from putatively immune individuals

proliferate to onchocercal antigens and produce

IL-5 and IFN-g in contrast to patients with

generalized onchocerciasis. The defective response

of the latter is due to production of the deactivating

cytokines IL-10 and TGF-ß. A T cell type resembling

the Th3 or Tr1 regulatory T cells has been

found in these patients. This T cell is specific for

O. volvulus and its task may be a specific inhibition

of T cell response by production of IL-10 and

TGF at the same time scavenging IL-2 (Doetze et

al. 2000).

The presence of endosymbiotic rickettsia-like

bacteria of the genus Wolbachia in most filarial

species has been known for more than 20 years.

Achim Hoerauf et al. (1999) discovered in murine

filariasis that these bacteria are susceptible to tetracycline

antibiotics and that their depletion from

the nematodes blocks worm development and abolishes

fertility. They also demonstrated tetracycline

to have no effect on the Wolbachia-free filaria

Acanthocheilonema viteae, demonstrating that the

antibiotic has no direct activity on nematodes. Then

they conducted a tetracyclin treatment study on onchocerciasis

patients in Ghana which showed that

bacterial depletion can be achieved long-term and

leads to a total and prolonged sterility of female

worms (Hoerauf et al. 2000). The efficacy thus

surpasses that of ivermectin and may render an anti-

Wolbachia therapy as a new option for the treatment

of filariasis. A combination therapy of doxycycline

and ivermectin resulted in a significantly

prolonged and enhanced amicrofilaridermia compared

to sole ivermectin treatment (Hoerauf et al.

unpublished). The finding that many of the pathogenetic

sequelae of onchocerciasis are due to reactivity

to Wolbachia antigen or LPS and not to O.

volvulus itself (Brattig et al. 2000) has a bearing

for the therapeutical interventions.

Aids research is also performed in a collaborative

effort of several departments. The distribution

of HIV is studied in the lymphoid tissue of patients

and the antibody response to major neutralizing

epitopes of HIV and the cellular immune response

are characterized. Recent data from the Department

of Pathology showed that the oral mucosal route is

a most efficient route of infection due to rapid infection

of oral mucosal-associated lymphoid tissue

in the simian immunodeficiency virus system

(Stahl-Hennig et al. 1999, Zhang et al. 1999a). The

quantification of HIV in the lymphoid tissue and

the enumeration of productively infected cells

showed that the unenlarged lymph nodes of HIV-

1-infected, asymptomatic patients with high CD4

T cell counts are sites for virus replication and CD4

T cell proliferation (Tenner-Racz et al. 1998). This

is found also in late stages of the disease and has

important implications for therapeutical strategies

(van Ende et al. 1999, Zhang et al. 1999b).

Malaria research is another program with institute-

wide cooperations. Ongoing projects characterize

the glutathione metabolism (Gilberger et

al. 2000) and polyamine synthesis of Plasmodium

falciparum. These studies demonstrate that the

plasmodicidal effect of an inhibitor of glutathion

synthesis does not depend on its specificity towards

its target enzyme in the parasite, but on the changed

physiological needs for the metabolite GSH in the

P. falciparum-infected RBCs. Therefore the depletion

of glutathione is proposed as a chemotherapeutic

strategy for malaria, and gamma-glutamylcysteine

synthetase is proposed as a potential

drug target (Luersen et al. 2000). P. falciparum in

contrast to other organisms presents a unique bifunctional

ornithine decarboxylase plus Sadenosylmethionine

decarboxylase, an organization

which is possibly exploitable for the design of

new antimalarial drugs (Muller et al. 2000).

Clinical studies on patients with severe malaria

have supported the notion that the immune response

of T cells may not be beneficial but rather

contribute to pathology (Schlotmann et al. 2000).

However, NO may have a beneficial rather than a

deleterious role in falciparum malaria (Chiwakata

et al. 2000). Ongoing work also characterizes the

repertoire of sporozoite gene expression in the

mosquito and the proteomics of rhoptry proteins.

A molecular genetic approach is presently used to

identify genes involved in susceptibility for or resistance

to severe malaria as well as to other tropical

infections such as onchocerciasis. This approach

involves the scanning of the genome in

families with defined manifestations of infectious

diseases.

Besides these major areas of research, a variety

of other agents and issues is investigated. These

include the regulation of heat-shock protein expression

in Leishmania. Novel heat shock proteins are

identified, their role in infectivity is determined by

genetic manipulation. Candidate target molecules

are identified for chemotherapy of filariasis and

malaria. Key enzymes involved in metabolism of

glutathion and polyamines in filariae are characterized

and cloned. Parasite-specific peculiarities

of such molecules are exploited as an approach for

rational drug design. Oligogenic linkage and segregation

analysis is performed to identify loci influencing

the intensity of infection with Schistosoma

mansoni and O. volvulus. The epidemiology

of filariasis and the occurence in the vectors is studied.

The immune response to Trypanosoma cruzi

in patients with Chagas disease is studied. The role

of different T cell subpopulations and the effect of

infections on the behaviour of antigen-presenting

cells by T. cruzi are studied. The immune response

to an effector mechanisms against T. cruzi and the

rodent filaria Litomosoides sigmodontis are analyzed

in mice (Al-Qaoud et al. 2000). The immune

mechanisms and possible targets for vaccination

and therapy are studied in such model systems.

Novel strategies of vaccination such as peptideloaded

heat shock proteins (Breloer et al. 1999)

may be promising in this respect.

The BNI is the only federal institute in the Federal

Republic of Germany equipped with a maximum

containment laboratory (BSL4) for work with

hemorrhagic fever viruses. The Institute performs

diagnostic tests for tropical virus infections and

pursues research on epidemiology, virology and

immunology of Lassavirus, Denguevirus and

Hantavirus infections (ter Meulen et al. 2000). The

recent imported cases of Lassa fever from West

Africa have demonstrated the essential role of the

BNI for the diagnosis and handling of such cases

in Germany.

OUTLOOK

In the century of the existence of BNI, parts of

tropical medicine have changed dramatically, modern

techniques in molecular biology, immunology

and genetics have changed the scientific look at a


parasite or a disease. In other parts, however, tropical

medicine faces the same problems as decades

ago. More and novel ones are to come. Overpopulation,

migration, globalization, megacities, mass

travel and rapid spread of infectious agents are

paradigms of future problems. At the beginning of

the second century of the existence of Instituto

Oswaldo Cruz and Bernhard Nocht Institute their

research on infectious diseases is needed as urgently

as ever. Today our generation has a number

of weapons against infectious agents at hand due

to the research financed by previous generations.

We owe it to the next generations not to cease in

the permanent effort to combat these diseases.

REFERENCES

Al-Qaoud KM, Pearlman E, Klukowski J, Hartung T,

Fleischer B, Hoerauf A 2000. Interleukin-5 is required

for neutrophil-mediated worm elimination in

murine filariasis. Int Immunol 12: 899-908.

Brattig NW, Rathjens U, Ernst M, Geisinger F, Renz A,

Tischendorf FW 2000. Lipopolysaccharide like

molecules derived from Wolbachia endobacteria of

the filaria Onchocerca volvulus are candidate mediators

in the sequence of inflammatory and antiinflammatory

responses of human monocytes. Microb

Infect 2, in press.

Breloer M, Fleischer B, von Bonin A 1999. In vivo and

in vitro activation of T cells following administration

of antigen-negative heat shock proteins. J

Immunol 162: 3141-3147.

Bruchhaus I, Jacobs T, Leippe M, Tannich E 1996. Entamoeba

histolytica and Entamoeba dispar: differences

in numbers and expression of cysteine proteinase

genes. Mol Microbiol 22: 255-263.

Chiwakata CB, Hemmer CJ, Dietrich M 2000. High levels

of inducible nitric oxide synthase mRNA are associated

with increased monocyte counts in blood

and have a beneficial role in Plasmodium falciparum

malaria. Infect Immun 68: 394-399.

Doetze A, Satoguina J, Burchard G, Rau T, Fleischer B,

Hoerauf A 2000. Antigen-specific cellular

hyporesponsiveness in generalized onchocerciasis

is mediated by Th3/Tr1-type cytokines IL-10 and

TGF-ß but not by a Th1 to Th2 shift. Int Immunol

12: 623-630.

Giemsa G, Godoy A 1909. Sobre a ultrafiltração.

Pesquisas tendentes a obter a concentração do soro

antidifterico. Ueber Filtration und Versuche, mit

Hilfe derselben Diphterieserum zu konzentrieren.

Mem Inst Oswaldo Cruz 1: 3-11.

Gilberger T, Schirmer RH, Walter RD, Muller S 2000.

Deletion of the parasite-specific insertions and mutation

of the catalytic triad in glutathione reductase

from chloroquine-sensitive Plasmodium falciparum

3D7. Mol Biochem Parasitol 107: 169-179.

Halberstaedter L, von Prowazek S 1909. Ueber

Chlamydozoenbefunde bei Blennorrhoea neonatorum

non gonorrhoica. Berl klin Wochenschr 46:

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Hamann L, Nickel R, Tannich E 1995. Transfixion and

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Hoerauf A, Nissen-Pähle K, Schmetz C, K H-D, Blaxter

ML, Büttner DW, Gallin MY, Al-Qaoud KM, Lucius

R, Fleischer B 1999. Tetracycline therapy targets

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Hoerauf A, Volkmann L, Hamelmann C, Adjei O,

Autenrieth IB, Fleischer B, Büttner DW 2000. Endosymbiotic

bacteria in worms as targets for a novel

chemotherapy in filariasis. Lancet 355: 1242-1243.

Lotter H, Zhang T, Seydel KB, Stanley SL Jr, Tannich

E 1997. Identification of an epitope on the Entamoeba

histolytica 170-kD lectin conferring antibodymediated

protection against invasive amebiasis. J

Exp Med 185: 1793-1801.

Luersen K, Walter RD, Muller S 2000. Plasmodium

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On October 1st 1900 the so-called Institut für Schiffs- und Tropenkrankheiten (Institute for Maritime and Tropical Diseases) came into being, today's Bernhard Nocht Institute for Tropical Medicine. After the founding of schools of tropical medicine in Liverpool and London in 1899, it was the third major European institute for training and research in tropical medicine to be established within a short time.

At the roots of the institute is the disastrous cholera outbreak that hit Hamburg in summer 1892 during the fifth cholera pandemic. The epidemic, which affected more than 17 000 people and claimed at least 9000 lives, spread through contaminated drinking water from the river Elbe to the city. It became famous as an example of the ignorance of the Hamburg authorities who, in spite of many warnings, shirked the expense of a water filtration system and, in the face of the outbreak, tried to conceal the situation from the public by all means.

Bernhard Nocht (1857–1945) was a navy doctor at that time and tasked with controlling ships to prevent the import of new cases. Nocht had extensive experience with cholera. He had been on a tour to East Asia in 1884 and, when his ship sank, stayed there for nearly two years. He had taken this opportunity to study tropical infections, particularly cholera. Because of this knowledge, Robert Koch had asked that Nocht be appointed to his newly founded Institute for Hygiene in Berlin from 1887 until 1890. Because of his proven ability, Nocht was offered the position of Chief Medical Officer of the Harbour of Hamburg, and he entered office in April 1893.

In charge of the hygiene of the harbour and all incoming ships, Nocht saw the great and increasing number of sailors and travellers with tropical diseases entering Hamburg by ship. In 1899, for example, Nocht reported 500 ships with 15 000 persons arriving from overseas in the port of Hamburg. On average, one in 16 of the sailors on steam ships had malaria, one in nine on sailing ships, and one in six on ships from West Africa. Tropical and other infections were common. For example, for the period 1895–1902, Nocht reported 1508 cases of malaria, 226 of typhoid fever, 10 cases of small-pox, 62 of dysentery, five of diphtheria, 264 of tuberculosis, 11 of scurvy and 91 of beriberi. In 1895, Nocht secured 25 beds in the Hamburg General Hospital to treat patients with tropical infections and there were plans to re-establish a previously existing Sailor's Hospital at the harbour.

Since tropical infections were largely unknown to German doctors, Nocht saw the necessity of establishing a training facility. He therefore tried to persuade the authorities of the need for an institute for research, training and therapy of tropical infections that should be located in the Hamburg harbour as the main port of entry of patients. Simultaneously, Robert Koch proposed such an institute – but affiliated with the Foreign Office, located in Berlin and connected to Berlin University. Germany had colonies since 1884, thus this idea was welcomed by the Colonial Department of the Foreign Office. In a meeting on January 31st 1899, Nocht, Koch and members of the Foreign Office initially decided that Berlin should be the location of the Institute for Tropical Medicine and that a proposal should be submitted to the imperial government. Nocht returned to Hamburg and asked the Hamburg authorities to provide the planned Sailor's Hospital with research laboratories and training facilities. These intentions led the Colonial Department to renounce the idea of an institute in Berlin and to support the plans in Hamburg. On January 15th, 1900 a proposal was brought to the Hamburg Parliament, and on 24 January it was decided that an Institute for Maritime and Tropical Diseases should be added to the Sailor's Hospital.

On 1 October 1900 the institute opened its doors. Nocht became director (he held this post until 1930) and was simultaneously Chief Physician of the hospital, in addition to performing his duties as Medical Officer of the Harbour. Only in 1906 did he resign from the office as harbour physician, but then was appointed Head of the Department of Health of the entire City of Hamburg from 1906 to 1919. After a few months the Institute had 24 members; six were scientists or physicians, three of them seconded from the army or the Colonial Department. Nocht's first associate was Gustav Giemsa (1867–1948), who led the Department of Chemistry (consisting of himself and one technical assistant) and began work on the detection of plasmodia in blood smears. Nocht had tried to modify the Romanowsky stain but was unable to get consistent results. By 1904 Giemsa had developed the reproducible method as it is still used today (Giemsa 1904).

Over the next few years Nocht recruited a very able group of scientists ( Figure 1). Friedrich Fülleborn (1866–1933) arrived in 1901, initially seconded from the army and later a permanent member of the Institute. He was in charge of teaching, soon became head of the Department of Helminthology, and in 1930, succeeded Nocht as director. Peter Mühlens (1874–1943) also joined in 1901 seconded from the navy, later to become chief physician of the hospital and director of the Institute in 1933. Fritz Schaudinn (1871–1906), the discoverer of Treponema pallidum, was appointed in 1906 as head of the Department of Protozoology because of his brilliant work on amoebae and amoebiasis. Tragically he died only months later, possibly due to a self-experiment with Entamoeba histolytica. His successor was Stanislaus von Prowazek (1875–1915). In September 1909 Nocht appointed Henrique da Rocha-Lima (1897–1956) as head of the new Department of Pathology. Da Rocha-Lima had previously led the Department of Pathology at the Instituto Oswaldo Cruz, at the age of 24! He remained in Hamburg until December 1927. Finally, the Department of Entomology was established, headed by Erich Martini (1880–1960).

Figure 1

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Members of the Institute for Maritime and Tropical Diseases in 1925. From left, front: Friedrich Fülleborn, Bernhard Nocht, Gustav Giemsa. Back: Henrique da Rocha-Lima, Peter Mühlens, Erich Martini, Eduard Reichenow, Manfred Mayer.

Training of physicians started in January 1901. Between 1901 and 1914, 43 courses with 836 participants were held. Upon Nocht's initiative the German Society for Tropical Medicine was founded in 1907, with Nocht as vice-president and later, president. By 1914, the Institute had seven scientists on its own payroll and four scientists funded by the army or colonial office. In that year the Institute moved to a new building on the north bank of the river Elbe where it still is today ( Figure 2). The building alone cost 1.5 m marks, its equipment and furnishings another 800 000 marks. The annual research budget in 1914 was 246 302 marks.

Figure 2

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The historical building of the BNI at the front of the harbour in 1921.

The Institute faced its first severe crisis in the years after 1918, when Germany had lost its colonies: in addition to financial problems, the necessity of its existence was questioned. It was the quality of the work performed at the Institute for Tropical Diseases that saved it in the end. When the University of Hamburg was founded in 1919, Nocht was appointed full professor of tropical medicine and in 1926, the university's rector. The Institute re-entered the international scientific community: Fülleborn was invited to the 1st American Congress of Tropical Medicine in 1924, and in 1927 Nocht was elected vice-president of the Committee for Hygiene of the League of Nations, the predecessor of the WHO. In 1942 the Institute was named Bernhard Nocht Institute (BNI) in honour of its founder.

The first decades of the BNI's history brought a number of major discoveries. The description of Rickettsia prowazeki, the agent of epidemic typhus, by da Rocha-Lima and von Prowazek was one such milestone. Both scientists became infected and von Prowazek died in 1915. da Rocha-Lima named the agent after his colleague and friend ( da Rocha-Lima 1916) . He later described another louse-transmitted infectious agent, Rickettsia (later Rochalimea, now Bartonella) quintana, the causative agent of trench fever. Von Prowazek also discovered the infectious origin of trachoma ( Halberstaedter & Prowazek 1909). As an animal model for the chemotherapy of malaria, avian malaria was established and found suitable to test new derivatives of quinine such as plasmochin and atebrin. Using this model, the protozoologist Eduard Reichenow and his co-workers described the extraerythrocytic development of plasmodial sporozoites as the missing link between the infective sporozoite and the infected erythrocyte ( Reichenow & Mudrow 1943). In 1931, the helminthologist Hans Vogel discovered the developmental cycle of Opisthorchis felineus ( Vogel 1934), and later proved, in experiments lasting from 1938 to 1950, the existence of acquired immunity to schistosomiasis ( Vogel & Minning 1953). In the 1950s Vogel discovered Paragonimus africanus and described Echinococcus multilocularis and its life-cycle as a new species ( Vogel 1955).

From 1933 to 1945 national socialist laws were imposed on the Institute. Jewish scientists had to leave, among them Manfred Mayer (1875–1951) who had been the Institute's bacteriologist since 1906, a renowned scientist honoured with the Bernhard Nocht Medal and an honorary doctoral degree from the University of Giessen in 1929. When Fülleborn died in 1933 from coronary heart disease it was assumed that the stressful situation had contributed to his early death. The government of the Reich tried to increase its influence due to re-emerging colonial ambitions. The institute was badly damaged in World War II during the heavy bombardment of Hamburg.

A century after its foundation the BNI remains Germany's largest research institute for tropical medicine. Affiliated to the Federal Ministry of Health and the Ministry of Health of the State of Hamburg, it is financed jointly by the Federal Government and the States of the Federal Republic of Germany.

The Institute conducts disease-orientated basic research and applies contemporary techniques of cell biology, molecular genetics, and immunology to the characterization of host–pathogen interactions in tropical infectious diseases. Research activities concentrate on three areas: cellular and molecular biology of infectious agents that cause tropical diseases; the host response to such agents and its role in protection and pathology; and a disease-orientated approach to pathogenesis and pathology. Accordingly, the studies focus on infectious diseases caused by parasites and tropical viruses. Main topics of work are the pathogenicity factors and cell biology of parasites, analysis of the host–parasite relationship including immunological defense mechanisms, and the definition of genes causing susceptibility to certain tropical infections. In all these ventures special emphasis is put on two issues: relevance for disease prevention and control, and use of tropical infections as models for general issues in medicine and biology.

To fulfil these aims the BNI has a specific organizational structure consisting of departments established for longer periods of time (e.g. Molecular Parasitology, Immunology, Virology or Molecular Medicine), a clinical department and a number of temporary research groups. Institute-wide research programs form the core of the scientific work, most of which directly or indirectly leads to projects participating in one of the programs. Programs have been established on important and exemplary diseases (Amoebiasis, Filariasis, Malaria and AIDS) to foster interdisciplinary communication and exchange of expertise leading to problem-orientated research. As an example, the Filariasis Program profits from concerted action in immunology, parasitology, molecular biology, genetics and biochemistry. In this program the induction of the immune response and the effector mechanisms against filaria are characterized in patients and in a mouse model; the specific immunosuppression in generalized onchocerciasis is analysed as a possible model for immunological tolerance; loci determining the genetic basis of different manifestations of onchocerciasis are defined by genome-wide linkage analysis; metabolic pathways of filariae are explored as targets for chemotherapy; endobacteria are exploited as targets of the immune response or of chemotherapy; and secreted worm proteins are examined for their possible role as pathogenicity factors. Epidemiologic studies determine prevalence, and well-defined patient groups in areas endemic for filariasis provide the basis for clinical studies and concomitant in vitro investigations.

The BNI cultivates cooperations and contacts with developing countries, mostly with African nations, but also in South America and Asia. Since 1997 the Institute has been maintaining a cooperative research centre in Kumasi, Ghana, so far mainly for research on onchocerciasis and malaria. This centre was set up according to a state agreement between the Republic of Ghana and the State of Hamburg, to establish long-standing contacts to scientists of the host country. Its hallmark is that each research project is carried out jointly by scientists from Hamburg and from Kumasi. Projects on Lassa fever and amoebiasis are presently pursued in Guinea and Vietnam, respectively.

Besides research, the BNI conducts various educational and service activities in the area of tropical medicine. Three members of the BNI hold full professorships at the University of Hamburg and are engaged in teaching. An annual three-month course on tropical medicine is officially accredited as a diploma course by the German Medical Board and the American Society of Tropical Medicine and Hygiene. The BNI Department of Clinical Medicine has 68 beds and an outpatient clinic; the BNI is equipped with the only true biosafety level four laboratory in Germany, and it performs diagnostic tests for the detection of parasites and haemorrhagic fever viruses.

In the course of the history of the BNI, the need for an institute for research in tropical medicine was repeatedly questioned. Today, however, at the beginning of the institute's second century, it is clear that basic and applied research on tropical infectious diseases is as urgently required as ever. Overpopulation, migration, globalization, megacities, mass travel and rapid spread of infectious agents are paradigms of the problems to come. This has recently been acknowledged again in Okinawa by the high priority the G8 assigned to programs combating malaria and other parasitic infections. The revolutionary development of biomedical technology will provide the tools to effectively fight these diseases.